Random seed is 1 Number of lambda values is 11 Temperature is 298.0 K Inverse temperature is 0.40350 (kJ/mol)^-1 1/ Inverse temperature is 2.47834 (kJ/mol) Output is verbose Number of blocks is 40 Allocating storage for energies... Reading data from files... Reading datafile data/trp11decorr.01.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.02.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.03.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.04.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.05.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.06.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.07.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.08.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.09.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.10.xvg into memory... Parsing energies from datafile... Reading datafile data/trp11decorr.11.xvg into memory... Parsing energies from datafile... Replica 1 / 40 Computing statistical inefficiencies: lambda 0: g = 2.291 lambda 1: g = 1.000 lambda 2: g = 2.517 lambda 3: g = 1.993 lambda 4: g = 1.869 lambda 5: g = 1.436 lambda 6: g = 1.542 lambda 7: g = 1.654 lambda 8: g = 2.130 lambda 9: g = 1.162 lambda 10: g = 1.210 Subsampling data to produce uncorrelated samples... number of samples per lambda: [374 234 479 347 496 500 355 134 335 358 400] Method: EXP Forward EXP: Interval 1, DeltaF=6.1537 +/- 0.6545, Sum=3.6451 +/- 0.2537 Interval 2, DeltaF=1.8781 +/- 0.3116, Sum=4.7575 +/- 0.2602 Interval 3, DeltaF=3.4732 +/- 0.4016, Sum=6.8148 +/- 0.2772 Interval 4, DeltaF=3.5625 +/- 0.5050, Sum=8.9250 +/- 0.3157 Interval 5, DeltaF=1.9975 +/- 0.5494, Sum=10.1083 +/- 0.3628 Interval 6, DeltaF=-0.3572 +/- 0.3323, Sum=9.8967 +/- 0.3686 Interval 7, DeltaF=-1.4840 +/- 0.4177, Sum=9.0176 +/- 0.3829 Interval 8, DeltaF=-2.4739 +/- 0.3873, Sum=7.5523 +/- 0.3930 Interval 9, DeltaF=-2.8937 +/- 0.2628, Sum=5.8382 +/- 0.3952 Interval 10, DeltaF=-1.1141 +/- 0.1838, Sum=5.1783 +/- 0.3957 Forward EXP free energy: 5.1783 +/- 0.3957 Reverse EXP: Interval 1, DeltaF=6.7330 +/- 0.6860, Sum=3.9882 +/- 0.2788 Interval 2, DeltaF=1.8850 +/- 0.2944, Sum=5.1047 +/- 0.2835 Interval 3, DeltaF=3.1594 +/- 0.3456, Sum=6.9762 +/- 0.2921 Interval 4, DeltaF=3.6046 +/- 0.3943, Sum=9.1113 +/- 0.3063 Interval 5, DeltaF=1.4517 +/- 0.4240, Sum=9.9712 +/- 0.3243 Interval 6, DeltaF=-0.5024 +/- 0.2916, Sum=9.6736 +/- 0.3282 Interval 7, DeltaF=-1.6476 +/- 0.4797, Sum=8.6977 +/- 0.3554 Interval 8, DeltaF=-2.3668 +/- 0.3104, Sum=7.2957 +/- 0.3599 Interval 9, DeltaF=-3.0314 +/- 0.2543, Sum=5.5001 +/- 0.3619 Interval 10, DeltaF=-1.1074 +/- 0.1796, Sum=4.8441 +/- 0.3624 Reverse EXP free energy: 4.8441 +/- 0.3624 Averge of forward and reverse EXP: Interval 1, DeltaF=6.4433 +/- 0.3463, Sum=3.8166 +/- 0.0710 Interval 2, DeltaF=1.8815 +/- 0.0708, Sum=4.9311 +/- 0.0711 Interval 3, DeltaF=3.3163 +/- 0.1092, Sum=6.8955 +/- 0.0715 Interval 4, DeltaF=3.5835 +/- 0.1626, Sum=9.0182 +/- 0.0732 Interval 5, DeltaF=1.7246 +/- 0.1912, Sum=10.0397 +/- 0.0763 Interval 6, DeltaF=-0.4298 +/- 0.0759, Sum=9.7852 +/- 0.0764 Interval 7, DeltaF=-1.5658 +/- 0.1572, Sum=8.8576 +/- 0.0778 Interval 8, DeltaF=-2.4204 +/- 0.0970, Sum=7.4240 +/- 0.0780 Interval 9, DeltaF=-2.9625 +/- 0.0515, Sum=5.6692 +/- 0.0780 Interval 10, DeltaF=-1.1108 +/- 0.0254, Sum=5.0112 +/- 0.0780 Average EXP free energy: 5.0112 +/- 0.0780 Interval 1, DeltaF=6.7330 +/- 0.3622, Sum=3.9882 +/- 0.0777 Interval 2, DeltaF=1.8781 +/- 0.4722, Sum=5.1006 +/- 0.1532 Interval 3, DeltaF=3.1594 +/- 0.5289, Sum=6.9721 +/- 0.2257 Interval 4, DeltaF=3.5625 +/- 0.5458, Sum=9.0823 +/- 0.2865 Interval 5, DeltaF=1.4517 +/- 0.5796, Sum=9.9422 +/- 0.3488 Interval 6, DeltaF=-0.3572 +/- 0.6720, Sum=9.7306 +/- 0.4396 Interval 7, DeltaF=-1.6476 +/- 0.6285, Sum=8.7547 +/- 0.4980 Interval 8, DeltaF=-2.4739 +/- 0.7129, Sum=7.2893 +/- 0.5819 Interval 9, DeltaF=-3.0314 +/- 0.6632, Sum=5.4937 +/- 0.6376 Interval 10, DeltaF=-1.1141 +/- 0.7266, Sum=4.8338 +/- 0.7101 Double-Wide EXP free energy: 4.8338 +/- 0.7101 Method: BAR Interval 1, DeltaF=6.6431 +/- 0.3403, Sum=3.9349 +/- 0.0686 Interval 2, DeltaF=1.8835 +/- 0.2106, Sum=5.0506 +/- 0.0735 Interval 3, DeltaF=3.2644 +/- 0.2522, Sum=6.9842 +/- 0.0826 Interval 4, DeltaF=3.4264 +/- 0.2945, Sum=9.0138 +/- 0.0972 Interval 5, DeltaF=1.2476 +/- 0.3088, Sum=9.7528 +/- 0.1124 Interval 6, DeltaF=-0.5187 +/- 0.2282, Sum=9.4456 +/- 0.1166 Interval 7, DeltaF=-1.6826 +/- 0.3071, Sum=8.4489 +/- 0.1293 Interval 8, DeltaF=-2.3866 +/- 0.2540, Sum=7.0352 +/- 0.1348 Interval 9, DeltaF=-2.9262 +/- 0.2080, Sum=5.3019 +/- 0.1372 Interval 10, DeltaF=-1.0946 +/- 0.1460, Sum=4.6535 +/- 0.1378 BAR free energy: 4.6535 +/- 0.1378 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.1951 +/- 0.5881, Sum=3.6696 +/- 0.2049 Interval 2, DeltaF=1.8930 +/- 0.2019, Sum=4.7909 +/- 0.2063 Interval 3, DeltaF=3.3614 +/- 0.3660, Sum=6.7819 +/- 0.2210 Interval 4, DeltaF=3.1642 +/- 0.3678, Sum=8.6562 +/- 0.2351 Interval 5, DeltaF=1.2394 +/- 0.3448, Sum=9.3904 +/- 0.2454 Interval 6, DeltaF=-0.5163 +/- 0.2161, Sum=9.0845 +/- 0.2470 Interval 7, DeltaF=-1.7015 +/- 0.2267, Sum=8.0767 +/- 0.2489 Interval 8, DeltaF=-2.3620 +/- 0.4306, Sum=6.6775 +/- 0.2720 Interval 9, DeltaF=-2.9802 +/- 0.3544, Sum=4.9123 +/- 0.2820 Interval 10, DeltaF=-1.0968 +/- 0.2202, Sum=4.2626 +/- 0.2835 Unopt. BAR free energy: 4.2626 +/- 0.2835 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6518 +/- 0.3392, Sum=3.9401 +/- 0.0682 Interval 2, DeltaF=1.8826 +/- 0.2173, Sum=5.0553 +/- 0.0737 Interval 3, DeltaF=3.2680 +/- 0.2577, Sum=6.9910 +/- 0.0835 Interval 4, DeltaF=3.4078 +/- 0.3045, Sum=9.0096 +/- 0.1000 Interval 5, DeltaF=1.2435 +/- 0.3159, Sum=9.7462 +/- 0.1161 Interval 6, DeltaF=-0.5184 +/- 0.2444, Sum=9.4391 +/- 0.1214 Interval 7, DeltaF=-1.6769 +/- 0.3233, Sum=8.4458 +/- 0.1363 Interval 8, DeltaF=-2.3799 +/- 0.2778, Sum=7.0361 +/- 0.1437 Interval 9, DeltaF=-2.9256 +/- 0.2073, Sum=5.3032 +/- 0.1460 Interval 10, DeltaF=-1.0945 +/- 0.1491, Sum=4.6548 +/- 0.1466 Postopt. BAR free energy: 4.6548 +/- 0.1466 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 608 N_k = [374 234] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.63948068] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.87197662] relative max_delta = 2.529766e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0543 relative max_delta = 3.606616e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6759 relative max_delta = 2.429127e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6431 relative max_delta = 4.945902e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6431 relative max_delta = 1.413466e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6431 relative max_delta = 1.101688e-13 Converged to tolerance of 1.101688e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6431 Final dimensionless free energies f_k = [ 0. 6.64306809] Computing normalized weights... Interval 1, DeltaF=6.6431 +/- 0.3403, Sum=3.9349 +/- 0.0686 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 713 N_k = [234 479] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.45642866] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.78238793] relative max_delta = 1.828778e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7924 relative max_delta = 5.575991e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.8826 relative max_delta = 4.789721e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.8835 relative max_delta = 5.255941e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.8835 relative max_delta = 6.608520e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.8835 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.8835 Final dimensionless free energies f_k = [ 0. 1.88354129] Computing normalized weights... Interval 2, DeltaF=1.8835 +/- 0.2106, Sum=5.0506 +/- 0.0735 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 826 N_k = [479 347] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.73547347] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.55687277] relative max_delta = 3.212515e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6325 relative max_delta = 2.873124e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3020 relative max_delta = 2.027584e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2645 relative max_delta = 1.150793e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2644 relative max_delta = 2.807470e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2644 relative max_delta = 1.706594e-10 Converged to tolerance of 1.706594e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2644 Final dimensionless free energies f_k = [ 0. 3.26436161] Computing normalized weights... Interval 3, DeltaF=3.2644 +/- 0.2522, Sum=6.9842 +/- 0.0826 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 843 N_k = [347 496] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.97452187] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.72126721] relative max_delta = 4.338346e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9258 relative max_delta = 1.061947e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6895 relative max_delta = 4.780384e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4320 relative max_delta = 7.501762e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4264 relative max_delta = 1.647787e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4264 relative max_delta = 8.437194e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4264 relative max_delta = 2.243528e-13 Converged to tolerance of 2.243528e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4264 Final dimensionless free energies f_k = [ 0. 3.42638254] Computing normalized weights... Interval 4, DeltaF=3.4264 +/- 0.2945, Sum=9.0138 +/- 0.0972 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 996 N_k = [496 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.32881186] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.58022418] relative max_delta = 4.333020e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6532 relative max_delta = 1.117366e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2968 relative max_delta = 4.962995e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2479 relative max_delta = 3.919396e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2476 relative max_delta = 2.475048e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2476 relative max_delta = 9.825640e-09 Converged to tolerance of 9.825640e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2476 Final dimensionless free energies f_k = [ 0. 1.24760651] Computing normalized weights... Interval 5, DeltaF=1.2476 +/- 0.3088, Sum=9.7528 +/- 0.1124 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 855 N_k = [500 355] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.33904557] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.45477739] relative max_delta = 2.544801e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4611 relative max_delta = 1.377240e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5184 relative max_delta = 1.103984e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5187 relative max_delta = 5.741222e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5187 relative max_delta = 1.597909e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5187 relative max_delta = 2.568715e-15 Converged to tolerance of 2.568715e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5187 Final dimensionless free energies f_k = [ 0. -0.5186514] Computing normalized weights... Interval 6, DeltaF=-0.5187 +/- 0.2282, Sum=9.4456 +/- 0.1166 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 489 N_k = [355 134] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97530102] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.36558021] relative max_delta = 2.857973e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3958 relative max_delta = 2.166821e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6706 relative max_delta = 1.644772e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6826 relative max_delta = 7.146353e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6826 relative max_delta = 1.340830e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6826 relative max_delta = 4.714004e-11 Converged to tolerance of 4.714004e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6826 Final dimensionless free energies f_k = [ 0. -1.6826483] Computing normalized weights... Interval 7, DeltaF=-1.6826 +/- 0.3071, Sum=8.4489 +/- 0.1293 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 469 N_k = [134 335] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.85665083] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.24058278] relative max_delta = 1.713536e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2555 relative max_delta = 6.611062e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3891 relative max_delta = 5.591699e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3866 relative max_delta = 1.024202e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3866 relative max_delta = 3.326351e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3866 relative max_delta = 3.479566e-14 Converged to tolerance of 3.479566e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3866 Final dimensionless free energies f_k = [ 0. -2.3866392] Computing normalized weights... Interval 8, DeltaF=-2.3866 +/- 0.2540, Sum=7.0352 +/- 0.1348 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 693 N_k = [335 358] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.26271944] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.76185339] relative max_delta = 1.807243e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7784 relative max_delta = 5.951307e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9270 relative max_delta = 5.076742e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9262 relative max_delta = 2.658819e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9262 relative max_delta = 4.876883e-09 Converged to tolerance of 4.876883e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9262 Final dimensionless free energies f_k = [ 0. -2.92620579] Computing normalized weights... Interval 9, DeltaF=-2.9262 +/- 0.2080, Sum=5.3019 +/- 0.1372 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 758 N_k = [358 400] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.0114732] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08799866] relative max_delta = 7.033598e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0887 relative max_delta = 6.046175e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0946 relative max_delta = 5.411894e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0946 relative max_delta = 8.967958e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0946 relative max_delta = 2.414014e-14 Converged to tolerance of 2.414014e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0946 Final dimensionless free energies f_k = [ 0. -1.09457965] Computing normalized weights... Interval 10, DeltaF=-1.0946 +/- 0.1460, Sum=4.6535 +/- 0.1378 Pairwise MBAR free energy: 4.6535 +/- 0.1378 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4012 N_k = [374 234 479 347 496 500 355 134 335 358 400] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.87751145 1.91465656 1.77679659 1.46751187 1.62727301 1.61835339 1.66945326 1.66714313 0.9659747 0.45091498] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.74057581 3.13858073 3.19217166 2.73532242 2.97339514 2.96532353 2.96305481 2.77324494 1.55054451 0.84918351] relative max_delta = 4.433894e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.9763 3.4940 4.0653 4.1706 4.5244 4.4746 4.3775 4.0152 2.5794 1.8354 relative max_delta = 3.428019e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.2393 6.8652 11.4055 16.3253 17.6827 17.2457 16.2215 14.1886 10.9028 9.7895 relative max_delta = 7.441364e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5548 8.5364 11.7498 15.6212 16.8560 16.3446 14.7375 12.3628 9.4019 8.3137 relative max_delta = 1.083191e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6392 8.5033 11.7939 15.2568 16.4905 15.9675 14.3125 11.9133 8.9739 7.8858 relative max_delta = 2.725782e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6367 8.5033 11.7861 15.2329 16.4671 15.9440 14.2887 11.8894 8.9501 7.8621 relative max_delta = 1.454853e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6367 8.5033 11.7861 15.2328 16.4670 15.9440 14.2886 11.8893 8.9500 7.8620 relative max_delta = 3.724944e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6367 8.5033 11.7861 15.2328 16.4670 15.9440 14.2886 11.8893 8.9500 7.8620 relative max_delta = 2.680829e-11 Converged to tolerance of 2.680829e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6367 8.5033 11.7861 15.2328 16.4670 15.9440 14.2886 11.8893 8.9500 7.8620 Final dimensionless free energies f_k = [ 0. 6.63671342 8.50331616 11.78612983 15.23278932 16.46703739 15.94397099 14.28859533 11.88933753 8.95004138 7.86199391] Computing normalized weights... DeltaMij: [[ 0. 3.9311732 5.03683172 6.98136485 9.02294998 9.75404121 9.44420944 8.46366862 7.04249863 5.30144375 4.6569526 ] [-3.9311732 0. 1.10565851 3.05019164 5.09177678 5.82286801 5.51303624 4.53249542 3.11132542 1.37027055 0.7257794 ] [-5.03683172 -1.10565851 0. 1.94453313 3.98611826 4.71720949 4.40737772 3.4268369 2.00566691 0.26461203 -0.37987912] [-6.98136485 -3.05019164 -1.94453313 0. 2.04158513 2.77267636 2.46284459 1.48230377 0.06113378 -1.6799211 -2.32441225] [-9.02294998 -5.09177678 -3.98611826 -2.04158513 0. 0.73109123 0.42125946 -0.55928136 -1.98045136 -3.72150623 -4.36599738] [-9.75404121 -5.82286801 -4.71720949 -2.77267636 -0.73109123 0. -0.30983177 -1.29037259 -2.71154258 -4.45259746 -5.09708861] [-9.44420944 -5.51303624 -4.40737772 -2.46284459 -0.42125946 0.30983177 0. -0.98054082 -2.40171082 -4.14276569 -4.78725684] [-8.46366862 -4.53249542 -3.4268369 -1.48230377 0.55928136 1.29037259 0.98054082 0. -1.42117 -3.16222487 -3.80671602] [-7.04249863 -3.11132542 -2.00566691 -0.06113378 1.98045136 2.71154258 2.40171082 1.42117 0. -1.74105488 -2.38554602] [-5.30144375 -1.37027055 -0.26461203 1.6799211 3.72150623 4.45259746 4.14276569 3.16222487 1.74105488 0. -0.64449115] [-4.6569526 -0.7257794 0.37987912 2.32441225 4.36599738 5.09708861 4.78725684 3.80671602 2.38554602 0.64449115 0. ]] dDeltaMij: [[ 0. 0.06638101 0.08081099 0.09199716 0.10781963 0.12558873 0.13286025 0.14601909 0.15762278 0.16273546 0.16450655] [ 0.06638101 0. 0.02435607 0.04892647 0.0746334 0.09857882 0.10768981 0.12355899 0.13707732 0.14292683 0.14494018] [ 0.08081099 0.02435607 0. 0.03473585 0.06661545 0.09265783 0.10229751 0.11888865 0.13288294 0.1389092 0.14097993] [ 0.09199716 0.04892647 0.03473585 0. 0.04924413 0.08102043 0.0918899 0.11006122 0.12504735 0.13143336 0.13362 ] [ 0.10781963 0.0746334 0.06661545 0.04924413 0. 0.05457679 0.06966319 0.09232075 0.10975628 0.11698004 0.1194316 ] [ 0.12558873 0.09857882 0.09265783 0.08102043 0.05457679 0. 0.03015697 0.06733835 0.08979625 0.09849373 0.10139315] [ 0.13286025 0.10768981 0.10229751 0.0918899 0.06966319 0.03015697 0. 0.04874909 0.07613989 0.08625958 0.08955694] [ 0.14601909 0.12355899 0.11888865 0.11006122 0.09232075 0.06733835 0.04874909 0. 0.03538822 0.05154943 0.05697586] [ 0.15762278 0.13707732 0.13288294 0.12504735 0.10975628 0.08979625 0.07613989 0.03538822 0. 0.02189936 0.03085975] [ 0.16273546 0.14292683 0.1389092 0.13143336 0.11698004 0.09849373 0.08625958 0.05154943 0.02189936 0. 0.01136697] [ 0.16450655 0.14494018 0.14097993 0.13362 0.1194316 0.10139315 0.08955694 0.05697586 0.03085975 0.01136697 0. ]] Replica 2 / 40 Computing statistical inefficiencies: lambda 0: g = 1.764 lambda 1: g = 1.093 lambda 2: g = 1.381 lambda 3: g = 2.102 lambda 4: g = 1.561 lambda 5: g = 1.965 lambda 6: g = 1.000 lambda 7: g = 1.000 lambda 8: g = 2.059 lambda 9: g = 1.422 lambda 10: g = 2.373 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 344 500 500 465 500 250 198 149 283 249] Method: EXP Forward EXP: Interval 1, DeltaF=6.4878 +/- 0.5816, Sum=3.8430 +/- 0.2003 Interval 2, DeltaF=1.9435 +/- 0.2655, Sum=4.9942 +/- 0.2046 Interval 3, DeltaF=2.5933 +/- 0.6825, Sum=6.5303 +/- 0.3435 Interval 4, DeltaF=3.8376 +/- 0.4467, Sum=8.8034 +/- 0.3633 Interval 5, DeltaF=2.2058 +/- 0.4038, Sum=10.1100 +/- 0.3759 Interval 6, DeltaF=-0.1469 +/- 0.3259, Sum=10.0230 +/- 0.3811 Interval 7, DeltaF=-2.3878 +/- 0.7742, Sum=8.6086 +/- 0.5209 Interval 8, DeltaF=-2.0024 +/- 0.3026, Sum=7.4225 +/- 0.5237 Interval 9, DeltaF=-3.1724 +/- 0.4098, Sum=5.5434 +/- 0.5330 Interval 10, DeltaF=-1.0662 +/- 0.1810, Sum=4.9118 +/- 0.5334 Forward EXP free energy: 4.9118 +/- 0.5334 Reverse EXP: Interval 1, DeltaF=7.3341 +/- 0.6013, Sum=4.3443 +/- 0.2141 Interval 2, DeltaF=1.9444 +/- 0.2677, Sum=5.4960 +/- 0.2183 Interval 3, DeltaF=3.4813 +/- 0.4374, Sum=7.5581 +/- 0.2460 Interval 4, DeltaF=3.4916 +/- 0.3623, Sum=9.6263 +/- 0.2580 Interval 5, DeltaF=1.3331 +/- 0.4154, Sum=10.4160 +/- 0.2775 Interval 6, DeltaF=-0.5662 +/- 0.3208, Sum=10.0806 +/- 0.2841 Interval 7, DeltaF=-1.4569 +/- 0.3793, Sum=9.2176 +/- 0.2966 Interval 8, DeltaF=-2.2159 +/- 0.3767, Sum=7.9051 +/- 0.3083 Interval 9, DeltaF=-3.0871 +/- 0.2617, Sum=6.0765 +/- 0.3109 Interval 10, DeltaF=-1.0526 +/- 0.2266, Sum=5.4530 +/- 0.3124 Reverse EXP free energy: 5.4530 +/- 0.3124 Averge of forward and reverse EXP: Interval 1, DeltaF=6.9110 +/- 0.2694, Sum=4.0936 +/- 0.0430 Interval 2, DeltaF=1.9439 +/- 0.0547, Sum=5.2451 +/- 0.0430 Interval 3, DeltaF=3.0373 +/- 0.2740, Sum=7.0442 +/- 0.0619 Interval 4, DeltaF=3.6646 +/- 0.1300, Sum=9.2149 +/- 0.0627 Interval 5, DeltaF=1.7695 +/- 0.1292, Sum=10.2630 +/- 0.0635 Interval 6, DeltaF=-0.3565 +/- 0.0805, Sum=10.0518 +/- 0.0636 Interval 7, DeltaF=-1.9224 +/- 0.3354, Sum=8.9131 +/- 0.0921 Interval 8, DeltaF=-2.1092 +/- 0.0919, Sum=7.6638 +/- 0.0923 Interval 9, DeltaF=-3.1297 +/- 0.0987, Sum=5.8099 +/- 0.0924 Interval 10, DeltaF=-1.0594 +/- 0.0332, Sum=5.1824 +/- 0.0924 Average EXP free energy: 5.1824 +/- 0.0924 Interval 1, DeltaF=7.3341 +/- 0.2782, Sum=4.3443 +/- 0.0459 Interval 2, DeltaF=1.9435 +/- 0.3721, Sum=5.4955 +/- 0.0940 Interval 3, DeltaF=3.4813 +/- 0.4273, Sum=7.5576 +/- 0.1433 Interval 4, DeltaF=3.8376 +/- 0.6496, Sum=9.8307 +/- 0.2881 Interval 5, DeltaF=1.3331 +/- 0.4923, Sum=10.6204 +/- 0.3219 Interval 6, DeltaF=-0.1469 +/- 0.6955, Sum=10.5334 +/- 0.4310 Interval 7, DeltaF=-1.4569 +/- 0.5336, Sum=9.6704 +/- 0.4628 Interval 8, DeltaF=-2.0024 +/- 0.9597, Sum=8.4843 +/- 0.7154 Interval 9, DeltaF=-3.0871 +/- 0.5689, Sum=6.6557 +/- 0.7406 Interval 10, DeltaF=-1.0662 +/- 0.9798, Sum=6.0242 +/- 0.9338 Double-Wide EXP free energy: 6.0242 +/- 0.9338 Method: BAR Interval 1, DeltaF=6.7299 +/- 0.3076, Sum=3.9864 +/- 0.0561 Interval 2, DeltaF=1.9385 +/- 0.2033, Sum=5.1346 +/- 0.0612 Interval 3, DeltaF=3.2457 +/- 0.2445, Sum=7.0571 +/- 0.0707 Interval 4, DeltaF=3.4850 +/- 0.2831, Sum=9.1214 +/- 0.0852 Interval 5, DeltaF=1.3091 +/- 0.3078, Sum=9.8968 +/- 0.1020 Interval 6, DeltaF=-0.4769 +/- 0.2447, Sum=9.6144 +/- 0.1080 Interval 7, DeltaF=-1.5811 +/- 0.2866, Sum=8.6778 +/- 0.1184 Interval 8, DeltaF=-2.2135 +/- 0.2743, Sum=7.3666 +/- 0.1265 Interval 9, DeltaF=-2.9310 +/- 0.2395, Sum=5.6305 +/- 0.1310 Interval 10, DeltaF=-1.0868 +/- 0.1579, Sum=4.9867 +/- 0.1318 BAR free energy: 4.9867 +/- 0.1318 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.5020 +/- 0.5313, Sum=3.8514 +/- 0.1672 Interval 2, DeltaF=1.9224 +/- 0.2343, Sum=4.9901 +/- 0.1703 Interval 3, DeltaF=3.0794 +/- 0.3222, Sum=6.8141 +/- 0.1811 Interval 4, DeltaF=3.3815 +/- 0.3727, Sum=8.8171 +/- 0.1989 Interval 5, DeltaF=1.3103 +/- 0.3415, Sum=9.5933 +/- 0.2106 Interval 6, DeltaF=-0.4999 +/- 0.2228, Sum=9.2971 +/- 0.2126 Interval 7, DeltaF=-1.5285 +/- 0.2787, Sum=8.3917 +/- 0.2175 Interval 8, DeltaF=-2.2092 +/- 0.3209, Sum=7.0831 +/- 0.2259 Interval 9, DeltaF=-3.0328 +/- 0.4666, Sum=5.2867 +/- 0.2601 Interval 10, DeltaF=-1.0843 +/- 0.2169, Sum=4.6445 +/- 0.2616 Unopt. BAR free energy: 4.6445 +/- 0.2616 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7294 +/- 0.3065, Sum=3.9861 +/- 0.0556 Interval 2, DeltaF=1.9394 +/- 0.2050, Sum=5.1349 +/- 0.0609 Interval 3, DeltaF=3.2330 +/- 0.2463, Sum=7.0499 +/- 0.0708 Interval 4, DeltaF=3.4779 +/- 0.2978, Sum=9.1099 +/- 0.0881 Interval 5, DeltaF=1.3079 +/- 0.3160, Sum=9.8847 +/- 0.1061 Interval 6, DeltaF=-0.4999 +/- 0.2228, Sum=9.5885 +/- 0.1101 Interval 7, DeltaF=-1.5954 +/- 0.2990, Sum=8.6435 +/- 0.1222 Interval 8, DeltaF=-2.2163 +/- 0.2715, Sum=7.3307 +/- 0.1298 Interval 9, DeltaF=-2.9299 +/- 0.2355, Sum=5.5952 +/- 0.1339 Interval 10, DeltaF=-1.0870 +/- 0.1565, Sum=4.9513 +/- 0.1346 Postopt. BAR free energy: 4.9513 +/- 0.1346 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 844 N_k = [500 344] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.68729561] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.91533576] relative max_delta = 2.498385e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1058 relative max_delta = 3.729736e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7986 relative max_delta = 2.489941e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7300 relative max_delta = 1.019329e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7299 relative max_delta = 1.335202e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7299 relative max_delta = 2.322330e-11 Converged to tolerance of 2.322330e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7299 Final dimensionless free energies f_k = [ 0. 6.7298816] Computing normalized weights... Interval 1, DeltaF=6.7299 +/- 0.3076, Sum=3.9864 +/- 0.0561 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 844 N_k = [344 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.47586026] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.81962697] relative max_delta = 1.889215e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8314 relative max_delta = 6.442864e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9378 relative max_delta = 5.488048e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9385 relative max_delta = 3.598822e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9385 relative max_delta = 1.739396e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.9385 relative max_delta = 9.163705e-16 Converged to tolerance of 9.163705e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9385 Final dimensionless free energies f_k = [ 0. 1.93847013] Computing normalized weights... Interval 2, DeltaF=1.9385 +/- 0.2033, Sum=5.1346 +/- 0.0612 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.64416706] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.46733442] relative max_delta = 3.336262e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5484 relative max_delta = 3.180608e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2699 relative max_delta = 2.206475e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2457 relative max_delta = 7.440951e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2457 relative max_delta = 3.495962e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2457 relative max_delta = 8.099931e-13 Converged to tolerance of 8.099931e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2457 Final dimensionless free energies f_k = [ 0. 3.24571682] Computing normalized weights... Interval 3, DeltaF=3.2457 +/- 0.2445, Sum=7.0571 +/- 0.0707 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 965 N_k = [500 465] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.99459722] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.75295805] relative max_delta = 4.326178e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9736 relative max_delta = 1.117824e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8448 relative max_delta = 4.866948e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4993 relative max_delta = 9.873866e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4850 relative max_delta = 4.110129e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4850 relative max_delta = 7.315030e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4850 relative max_delta = 2.318607e-11 Converged to tolerance of 2.318607e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4850 Final dimensionless free energies f_k = [ 0. 3.48495839] Computing normalized weights... Interval 4, DeltaF=3.4850 +/- 0.2831, Sum=9.1214 +/- 0.0852 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 965 N_k = [465 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.35787182] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.62756031] relative max_delta = 4.297412e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7015 relative max_delta = 1.054392e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3551 relative max_delta = 4.823175e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3093 relative max_delta = 3.498819e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3091 relative max_delta = 1.887915e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3091 relative max_delta = 5.474268e-09 Converged to tolerance of 5.474268e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3091 Final dimensionless free energies f_k = [ 0. 1.30907551] Computing normalized weights... Interval 5, DeltaF=1.3091 +/- 0.3078, Sum=9.8968 +/- 0.1020 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 750 N_k = [500 250] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.30510119] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.41346147] relative max_delta = 2.620807e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4197 relative max_delta = 1.497231e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4764 relative max_delta = 1.189495e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4769 relative max_delta = 9.918050e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4769 relative max_delta = 6.953828e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4769 relative max_delta = 3.375681e-15 Converged to tolerance of 3.375681e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4769 Final dimensionless free energies f_k = [ 0. -0.47688841] Computing normalized weights... Interval 6, DeltaF=-0.4769 +/- 0.2447, Sum=9.6144 +/- 0.1080 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 448 N_k = [250 198] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9832725] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.33564736] relative max_delta = 2.638233e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3598 relative max_delta = 1.775726e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5778 relative max_delta = 1.381721e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5811 relative max_delta = 2.097260e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5811 relative max_delta = 5.434350e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5811 relative max_delta = 3.721531e-14 Converged to tolerance of 3.721531e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5811 Final dimensionless free energies f_k = [ 0. -1.58111861] Computing normalized weights... Interval 7, DeltaF=-1.5811 +/- 0.2866, Sum=8.6778 +/- 0.1184 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 347 N_k = [198 149] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.53621306] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.99276774] relative max_delta = 2.291058e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0147 relative max_delta = 1.089421e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2124 relative max_delta = 8.937237e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2135 relative max_delta = 4.950214e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2135 relative max_delta = 2.136951e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2135 relative max_delta = 2.006236e-16 Converged to tolerance of 2.006236e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2135 Final dimensionless free energies f_k = [ 0. -2.21354403] Computing normalized weights... Interval 8, DeltaF=-2.2135 +/- 0.2743, Sum=7.3666 +/- 0.1265 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 432 N_k = [149 283] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.30572761] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.7791603] relative max_delta = 1.703510e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7947 relative max_delta = 5.545168e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9335 relative max_delta = 4.733262e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9310 relative max_delta = 8.396665e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9310 relative max_delta = 2.499942e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9310 relative max_delta = 2.393893e-14 Converged to tolerance of 2.393893e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9310 Final dimensionless free energies f_k = [ 0. -2.9310459] Computing normalized weights... Interval 9, DeltaF=-2.9310 +/- 0.2395, Sum=5.6305 +/- 0.1310 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 532 N_k = [283 249] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00351807] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08046665] relative max_delta = 7.121791e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0811 relative max_delta = 5.887762e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0868 relative max_delta = 5.271217e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0868 relative max_delta = 7.098820e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0868 relative max_delta = 1.123674e-14 Converged to tolerance of 1.123674e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0868 Final dimensionless free energies f_k = [ 0. -1.08683288] Computing normalized weights... Interval 10, DeltaF=-1.0868 +/- 0.1579, Sum=4.9867 +/- 0.1318 Pairwise MBAR free energy: 4.9867 +/- 0.1318 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3938 N_k = [500 344 500 500 465 500 250 198 149 283 249] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89994638 1.87713231 1.78644659 1.47529369 1.53417106 1.54432856 1.53755146 1.46235911 0.8585689 0.39902113] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.78400564 3.11718306 3.2393323 2.75543315 2.81977325 2.80533879 2.70831992 2.44588407 1.39776388 0.75661111] relative max_delta = 4.485139e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0405 3.5075 4.1115 4.2376 4.4475 4.3958 4.1947 3.7739 2.5173 1.8275 relative max_delta = 3.659915e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5066 7.1995 11.5787 16.8032 18.2730 17.8755 16.6801 14.7271 11.5954 10.4783 relative max_delta = 7.566063e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7183 8.7881 11.9613 15.9198 17.2175 16.7600 15.2269 12.9927 10.0826 8.9969 relative max_delta = 1.007351e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7400 8.6834 11.9428 15.4307 16.7227 16.2595 14.7141 12.4579 9.5682 8.4817 relative max_delta = 3.197951e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7387 8.6833 11.9351 15.3948 16.6877 16.2245 14.6791 12.4228 9.5331 8.4467 relative max_delta = 2.153717e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7387 8.6833 11.9351 15.3946 16.6875 16.2244 14.6789 12.4226 9.5330 8.4465 relative max_delta = 9.602159e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7387 8.6833 11.9351 15.3946 16.6875 16.2244 14.6789 12.4226 9.5330 8.4465 relative max_delta = 2.144231e-10 Converged to tolerance of 2.144231e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7387 8.6833 11.9351 15.3946 16.6875 16.2244 14.6789 12.4226 9.5330 8.4465 Final dimensionless free energies f_k = [ 0. 6.73867741 8.68332506 11.93508217 15.39463155 16.68752732 16.22435043 14.67890168 12.42260183 9.53299155 8.44650276] Computing normalized weights... DeltaMij: [[ 0. 3.99157029 5.14345771 7.06959488 9.11881518 9.88464562 9.61028866 8.69486165 7.35837099 5.6467469 5.00317902] [-3.99157029 0. 1.15188742 3.0780246 5.12724489 5.89307534 5.61871837 4.70329136 3.3668007 1.65517662 1.01160873] [-5.14345771 -1.15188742 0. 1.92613717 3.97535747 4.74118791 4.46683095 3.55140394 2.21491328 0.50328919 -0.14027869] [-7.06959488 -3.0780246 -1.92613717 0. 2.0492203 2.81505074 2.54069378 1.62526676 0.2887761 -1.42284798 -2.06641586] [-9.11881518 -5.12724489 -3.97535747 -2.0492203 0. 0.76583044 0.49147348 -0.42395353 -1.7604442 -3.47206828 -4.11563616] [-9.88464562 -5.89307534 -4.74118791 -2.81505074 -0.76583044 0. -0.27435697 -1.18978398 -2.52627464 -4.23789872 -4.8814666 ] [-9.61028866 -5.61871837 -4.46683095 -2.54069378 -0.49147348 0.27435697 0. -0.91542701 -2.25191767 -3.96354175 -4.60710964] [-8.69486165 -4.70329136 -3.55140394 -1.62526676 0.42395353 1.18978398 0.91542701 0. -1.33649066 -3.04811474 -3.69168263] [-7.35837099 -3.3668007 -2.21491328 -0.2887761 1.7604442 2.52627464 2.25191767 1.33649066 0. -1.71162408 -2.35519196] [-5.6467469 -1.65517662 -0.50328919 1.42284798 3.47206828 4.23789872 3.96354175 3.04811474 1.71162408 0. -0.64356788] [-5.00317902 -1.01160873 0.14027869 2.06641586 4.11563616 4.8814666 4.60710964 3.69168263 2.35519196 0.64356788 0. ]] dDeltaMij: [[ 0. 0.05359617 0.06740013 0.07892956 0.09454251 0.1146674 0.12346437 0.13773313 0.15083891 0.1591327 0.16208889] [ 0.05359617 0. 0.02283102 0.04584584 0.06941952 0.09502454 0.10547273 0.12186657 0.13650431 0.14561684 0.14884171] [ 0.06740013 0.02283102 0. 0.03215118 0.06157626 0.08945662 0.10048541 0.11757671 0.13268853 0.14204607 0.14535018] [ 0.07892956 0.04584584 0.03215118 0. 0.04600449 0.07949237 0.09172778 0.11018592 0.12618598 0.1359917 0.13943935] [ 0.09454251 0.06941952 0.06157626 0.04600449 0. 0.05477109 0.07133783 0.09389742 0.11224372 0.1231645 0.12696096] [ 0.1146674 0.09502454 0.08945662 0.07949237 0.05477109 0. 0.03324044 0.06907689 0.09250623 0.10548842 0.1098971 ] [ 0.12346437 0.10547273 0.10048541 0.09172778 0.07133783 0.03324044 0. 0.04665206 0.07654309 0.09188931 0.09692028] [ 0.13773313 0.12186657 0.11757671 0.11018592 0.09389742 0.06907689 0.04665206 0. 0.03974369 0.06239289 0.06962317] [ 0.15083891 0.13650431 0.13268853 0.12618598 0.11224372 0.09250623 0.07654309 0.03974369 0. 0.02890084 0.03987039] [ 0.1591327 0.14561684 0.14204607 0.1359917 0.1231645 0.10548842 0.09188931 0.06239289 0.02890084 0. 0.01409497] [ 0.16208889 0.14884171 0.14535018 0.13943935 0.12696096 0.1098971 0.09692028 0.06962317 0.03987039 0.01409497 0. ]] Replica 3 / 40 Computing statistical inefficiencies: lambda 0: g = 1.626 lambda 1: g = 1.426 lambda 2: g = 1.778 lambda 3: g = 3.375 lambda 4: g = 2.584 lambda 5: g = 2.775 lambda 6: g = 1.329 lambda 7: g = 1.260 lambda 8: g = 1.791 lambda 9: g = 1.399 lambda 10: g = 2.443 Subsampling data to produce uncorrelated samples... number of samples per lambda: [325 446 487 500 500 500 404 228 275 500 433] Method: EXP Forward EXP: Interval 1, DeltaF=6.8474 +/- 0.4674, Sum=4.0560 +/- 0.1294 Interval 2, DeltaF=2.0356 +/- 0.2438, Sum=5.2617 +/- 0.1341 Interval 3, DeltaF=3.3972 +/- 0.3164, Sum=7.2740 +/- 0.1466 Interval 4, DeltaF=3.6174 +/- 0.5388, Sum=9.4168 +/- 0.2260 Interval 5, DeltaF=2.0669 +/- 0.3911, Sum=10.6410 +/- 0.2435 Interval 6, DeltaF=-0.5994 +/- 0.3520, Sum=10.2860 +/- 0.2543 Interval 7, DeltaF=-1.7312 +/- 0.4514, Sum=9.2606 +/- 0.2815 Interval 8, DeltaF=-2.1745 +/- 0.3140, Sum=7.9725 +/- 0.2875 Interval 9, DeltaF=-2.7055 +/- 0.2987, Sum=6.3699 +/- 0.2923 Interval 10, DeltaF=-1.0530 +/- 0.1600, Sum=5.7462 +/- 0.2927 Forward EXP free energy: 5.7462 +/- 0.2927 Reverse EXP: Interval 1, DeltaF=6.6606 +/- 0.5122, Sum=3.9453 +/- 0.1554 Interval 2, DeltaF=2.1285 +/- 0.3070, Sum=5.2061 +/- 0.1651 Interval 3, DeltaF=3.1437 +/- 0.3874, Sum=7.0683 +/- 0.1875 Interval 4, DeltaF=3.1793 +/- 0.3609, Sum=8.9515 +/- 0.2028 Interval 5, DeltaF=1.0940 +/- 0.4068, Sum=9.5995 +/- 0.2252 Interval 6, DeltaF=-0.4635 +/- 0.2851, Sum=9.3249 +/- 0.2303 Interval 7, DeltaF=-1.6367 +/- 0.3781, Sum=8.3555 +/- 0.2454 Interval 8, DeltaF=-1.9726 +/- 0.3218, Sum=7.1870 +/- 0.2529 Interval 9, DeltaF=-3.0046 +/- 0.2460, Sum=5.4073 +/- 0.2555 Interval 10, DeltaF=-1.1021 +/- 0.1831, Sum=4.7544 +/- 0.2562 Reverse EXP free energy: 4.7544 +/- 0.2562 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7540 +/- 0.1858, Sum=4.0007 +/- 0.0204 Interval 2, DeltaF=2.0821 +/- 0.0606, Sum=5.2339 +/- 0.0206 Interval 3, DeltaF=3.2704 +/- 0.0982, Sum=7.1712 +/- 0.0213 Interval 4, DeltaF=3.3984 +/- 0.1731, Sum=9.1841 +/- 0.0278 Interval 5, DeltaF=1.5804 +/- 0.1226, Sum=10.1203 +/- 0.0292 Interval 6, DeltaF=-0.5315 +/- 0.0806, Sum=9.8055 +/- 0.0294 Interval 7, DeltaF=-1.6839 +/- 0.1355, Sum=8.8080 +/- 0.0314 Interval 8, DeltaF=-2.0736 +/- 0.0778, Sum=7.5798 +/- 0.0316 Interval 9, DeltaF=-2.8551 +/- 0.0587, Sum=5.8886 +/- 0.0316 Interval 10, DeltaF=-1.0776 +/- 0.0230, Sum=5.2503 +/- 0.0316 Average EXP free energy: 5.2503 +/- 0.0316 Interval 1, DeltaF=6.6606 +/- 0.2019, Sum=3.9453 +/- 0.0241 Interval 2, DeltaF=2.0356 +/- 0.2421, Sum=5.1511 +/- 0.0423 Interval 3, DeltaF=3.1437 +/- 0.3247, Sum=7.0132 +/- 0.0754 Interval 4, DeltaF=3.6174 +/- 0.3500, Sum=9.1559 +/- 0.1047 Interval 5, DeltaF=1.0940 +/- 0.3938, Sum=9.8039 +/- 0.1392 Interval 6, DeltaF=-0.5994 +/- 0.4574, Sum=9.4489 +/- 0.1864 Interval 7, DeltaF=-1.6367 +/- 0.4373, Sum=8.4794 +/- 0.2181 Interval 8, DeltaF=-2.1745 +/- 0.5228, Sum=7.1914 +/- 0.2716 Interval 9, DeltaF=-3.0046 +/- 0.4671, Sum=5.4116 +/- 0.3008 Interval 10, DeltaF=-1.0530 +/- 0.5374, Sum=4.7879 +/- 0.3461 Double-Wide EXP free energy: 4.7879 +/- 0.3461 Method: BAR Interval 1, DeltaF=6.7300 +/- 0.3109, Sum=3.9864 +/- 0.0572 Interval 2, DeltaF=1.9775 +/- 0.1999, Sum=5.1578 +/- 0.0619 Interval 3, DeltaF=3.1801 +/- 0.2490, Sum=7.0414 +/- 0.0720 Interval 4, DeltaF=3.2129 +/- 0.2860, Sum=8.9446 +/- 0.0868 Interval 5, DeltaF=1.0778 +/- 0.3170, Sum=9.5830 +/- 0.1052 Interval 6, DeltaF=-0.5889 +/- 0.2281, Sum=9.2341 +/- 0.1097 Interval 7, DeltaF=-1.6696 +/- 0.2718, Sum=8.2452 +/- 0.1181 Interval 8, DeltaF=-2.1347 +/- 0.2451, Sum=6.9807 +/- 0.1233 Interval 9, DeltaF=-2.8066 +/- 0.2104, Sum=5.3182 +/- 0.1261 Interval 10, DeltaF=-1.0832 +/- 0.1382, Sum=4.6766 +/- 0.1266 BAR free energy: 4.6766 +/- 0.1266 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8065 +/- 0.4481, Sum=4.0318 +/- 0.1189 Interval 2, DeltaF=1.9861 +/- 0.2534, Sum=5.2082 +/- 0.1249 Interval 3, DeltaF=3.1831 +/- 0.3202, Sum=7.0937 +/- 0.1388 Interval 4, DeltaF=3.2290 +/- 0.3611, Sum=9.0064 +/- 0.1589 Interval 5, DeltaF=1.0549 +/- 0.3436, Sum=9.6313 +/- 0.1736 Interval 6, DeltaF=-0.5643 +/- 0.2173, Sum=9.2970 +/- 0.1758 Interval 7, DeltaF=-1.6347 +/- 0.2419, Sum=8.3287 +/- 0.1792 Interval 8, DeltaF=-2.0272 +/- 0.3287, Sum=7.1280 +/- 0.1903 Interval 9, DeltaF=-2.9399 +/- 0.3846, Sum=5.3866 +/- 0.2095 Interval 10, DeltaF=-1.0934 +/- 0.1869, Sum=4.7389 +/- 0.2105 Unopt. BAR free energy: 4.7389 +/- 0.2105 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7320 +/- 0.3148, Sum=3.9876 +/- 0.0587 Interval 2, DeltaF=1.9777 +/- 0.2001, Sum=5.1591 +/- 0.0633 Interval 3, DeltaF=3.1771 +/- 0.2496, Sum=7.0410 +/- 0.0733 Interval 4, DeltaF=3.2115 +/- 0.2910, Sum=8.9433 +/- 0.0888 Interval 5, DeltaF=1.0751 +/- 0.3191, Sum=9.5802 +/- 0.1074 Interval 6, DeltaF=-0.6064 +/- 0.2403, Sum=9.2210 +/- 0.1127 Interval 7, DeltaF=-1.6773 +/- 0.2830, Sum=8.2275 +/- 0.1222 Interval 8, DeltaF=-2.1281 +/- 0.2467, Sum=6.9669 +/- 0.1275 Interval 9, DeltaF=-2.7979 +/- 0.2017, Sum=5.3096 +/- 0.1297 Interval 10, DeltaF=-1.0841 +/- 0.1367, Sum=4.6674 +/- 0.1302 Postopt. BAR free energy: 4.6674 +/- 0.1302 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 771 N_k = [325 446] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.58888699] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.88269229] relative max_delta = 2.649778e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0595 relative max_delta = 3.495173e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6563 relative max_delta = 2.398897e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7297 relative max_delta = 1.090735e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7300 relative max_delta = 4.590287e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7300 relative max_delta = 8.210436e-10 Converged to tolerance of 8.210436e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7300 Final dimensionless free energies f_k = [ 0. 6.73002498] Computing normalized weights... Interval 1, DeltaF=6.7300 +/- 0.3109, Sum=3.9864 +/- 0.0572 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 933 N_k = [446 487] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.50569063] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.85163897] relative max_delta = 1.868336e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8642 relative max_delta = 6.735787e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9772 relative max_delta = 5.717440e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9775 relative max_delta = 1.107214e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9775 relative max_delta = 6.193867e-10 Converged to tolerance of 6.193867e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9775 Final dimensionless free energies f_k = [ 0. 1.97746246] Computing normalized weights... Interval 2, DeltaF=1.9775 +/- 0.1999, Sum=5.1578 +/- 0.0619 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 987 N_k = [487 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.59353211] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.3980119] relative max_delta = 3.354778e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4786 relative max_delta = 3.249529e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1972 relative max_delta = 2.247802e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1801 relative max_delta = 5.399877e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1801 relative max_delta = 6.677023e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1801 relative max_delta = 9.915036e-15 Converged to tolerance of 9.915036e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1801 Final dimensionless free energies f_k = [ 0. 3.18005224] Computing normalized weights... Interval 3, DeltaF=3.1801 +/- 0.2490, Sum=7.0414 +/- 0.0720 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.93318248] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.63638518] relative max_delta = 4.297293e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8242 relative max_delta = 1.029345e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.4432 relative max_delta = 4.702153e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2180 relative max_delta = 6.997030e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2129 relative max_delta = 1.598194e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2129 relative max_delta = 8.317640e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.2129 relative max_delta = 2.264059e-13 Converged to tolerance of 2.264059e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2129 Final dimensionless free energies f_k = [ 0. 3.21289389] Computing normalized weights... Interval 4, DeltaF=3.2129 +/- 0.2860, Sum=8.9446 +/- 0.0868 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.2720757] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.48089473] relative max_delta = 4.342302e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5449 relative max_delta = 1.174742e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.1124 relative max_delta = 5.101541e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0779 relative max_delta = 3.199224e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0778 relative max_delta = 1.386237e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0778 relative max_delta = 2.579963e-09 Converged to tolerance of 2.579963e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0778 Final dimensionless free energies f_k = [ 0. 1.07777091] Computing normalized weights... Interval 5, DeltaF=1.0778 +/- 0.3170, Sum=9.5830 +/- 0.1052 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 904 N_k = [500 404] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.37884134] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.51118273] relative max_delta = 2.588925e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5189 relative max_delta = 1.488187e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5885 relative max_delta = 1.182514e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5889 relative max_delta = 6.763465e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5889 relative max_delta = 2.304888e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5889 relative max_delta = 9.614872e-15 Converged to tolerance of 9.614872e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5889 Final dimensionless free energies f_k = [ 0. -0.5888937] Computing normalized weights... Interval 6, DeltaF=-0.5889 +/- 0.2281, Sum=9.2341 +/- 0.1097 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 632 N_k = [404 228] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99143628] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.37739682] relative max_delta = 2.802101e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4058 relative max_delta = 2.021592e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6630 relative max_delta = 1.546458e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6696 relative max_delta = 3.935956e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6696 relative max_delta = 2.714900e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6696 relative max_delta = 1.293246e-12 Converged to tolerance of 1.293246e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6696 Final dimensionless free energies f_k = [ 0. -1.66956727] Computing normalized weights... Interval 7, DeltaF=-1.6696 +/- 0.2718, Sum=8.2452 +/- 0.1181 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 503 N_k = [228 275] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.56297583] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.96036005] relative max_delta = 2.027098e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.9779 relative max_delta = 8.869331e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.1356 relative max_delta = 7.382436e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.1347 relative max_delta = 3.893942e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.1347 relative max_delta = 7.959040e-09 Converged to tolerance of 7.959040e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.1347 Final dimensionless free energies f_k = [ 0. -2.13472773] Computing normalized weights... Interval 8, DeltaF=-2.1347 +/- 0.2451, Sum=6.9807 +/- 0.1233 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 775 N_k = [275 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.14144655] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.63357865] relative max_delta = 1.868682e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.6513 relative max_delta = 6.673378e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8097 relative max_delta = 5.639273e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8066 relative max_delta = 1.103995e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8066 relative max_delta = 3.965784e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8066 relative max_delta = 5.158272e-14 Converged to tolerance of 5.158272e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8066 Final dimensionless free energies f_k = [ 0. -2.80661973] Computing normalized weights... Interval 9, DeltaF=-2.8066 +/- 0.2104, Sum=5.3182 +/- 0.1261 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 933 N_k = [500 433] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99814189] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07651954] relative max_delta = 7.280653e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0772 relative max_delta = 6.192815e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0832 relative max_delta = 5.542848e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0832 relative max_delta = 9.012542e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0832 relative max_delta = 1.947415e-14 Converged to tolerance of 1.947415e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0832 Final dimensionless free energies f_k = [ 0. -1.08319156] Computing normalized weights... Interval 10, DeltaF=-1.0832 +/- 0.1382, Sum=4.6766 +/- 0.1266 Pairwise MBAR free energy: 4.6766 +/- 0.1266 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4598 N_k = [325 446 487 500 500 500 404 228 275 500 433] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.03160457 2.10720237 1.98725866 1.76485302 1.88660946 1.88061826 1.87931226 1.82039648 1.20051241 0.71383685] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.0538504 3.50773966 3.57753393 3.24971838 3.42025874 3.3907912 3.29721085 3.05138861 1.97643011 1.3101284 ] relative max_delta = 4.445172e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3019 3.8805 4.4165 4.6112 4.8941 4.8168 4.6132 4.2113 2.9345 2.2244 relative max_delta = 3.011466e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.6913 7.4343 11.6751 16.1963 17.4581 16.9416 15.6888 13.7896 10.7040 9.6097 relative max_delta = 7.196659e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7004 8.7680 11.9302 15.4645 16.6041 16.0305 14.4336 12.2499 9.3859 8.3230 relative max_delta = 9.273071e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7779 8.7537 11.9557 15.1899 16.3292 15.7508 14.1435 11.9381 9.0927 8.0291 relative max_delta = 1.909232e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7772 8.7538 11.9534 15.1775 16.3173 15.7388 14.1315 11.9260 9.0808 8.0171 relative max_delta = 7.598135e-04 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7772 8.7538 11.9534 15.1775 16.3172 15.7388 14.1315 11.9260 9.0807 8.0171 relative max_delta = 1.004613e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7772 8.7538 11.9534 15.1775 16.3172 15.7388 14.1315 11.9260 9.0807 8.0171 relative max_delta = 1.815956e-12 Converged to tolerance of 1.815956e-12 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7772 8.7538 11.9534 15.1775 16.3172 15.7388 14.1315 11.9260 9.0807 8.0171 Final dimensionless free energies f_k = [ 0. 6.77724851 8.7537566 11.95340602 15.1775151 16.31724743 15.73877173 14.13151593 11.92601857 9.08073734 8.01705147] Computing normalized weights... DeltaMij: [[ 0. 4.01441739 5.18517695 7.08044878 8.990209 9.66531502 9.32266226 8.37062463 7.06422617 5.37885985 4.74879898] [-4.01441739 0. 1.17075956 3.0660314 4.97579161 5.65089763 5.30824487 4.35620724 3.04980879 1.36444246 0.73438159] [-5.18517695 -1.17075956 0. 1.89527184 3.80503205 4.48013808 4.13748531 3.18544768 1.87904923 0.1936829 -0.43637796] [-7.08044878 -3.0660314 -1.89527184 0. 1.90976022 2.58486624 2.24221348 1.29017585 -0.01622261 -1.70158894 -2.3316498 ] [-8.990209 -4.97579161 -3.80503205 -1.90976022 0. 0.67510602 0.33245326 -0.61958437 -1.92598282 -3.61134915 -4.24141002] [-9.66531502 -5.65089763 -4.48013808 -2.58486624 -0.67510602 0. -0.34265276 -1.29469039 -2.60108885 -4.28645518 -4.91651604] [-9.32266226 -5.30824487 -4.13748531 -2.24221348 -0.33245326 0.34265276 0. -0.95203763 -2.25843609 -3.94380241 -4.57386328] [-8.37062463 -4.35620724 -3.18544768 -1.29017585 0.61958437 1.29469039 0.95203763 0. -1.30639846 -2.99176478 -3.62182565] [-7.06422617 -3.04980879 -1.87904923 0.01622261 1.92598282 2.60108885 2.25843609 1.30639846 0. -1.68536633 -2.31542719] [-5.37885985 -1.36444246 -0.1936829 1.70158894 3.61134915 4.28645518 3.94380241 2.99176478 1.68536633 0. -0.63006086] [-4.74879898 -0.73438159 0.43637796 2.3316498 4.24141002 4.91651604 4.57386328 3.62182565 2.31542719 0.63006086 0. ]] dDeltaMij: [[ 0. 0.05561617 0.06791453 0.07991134 0.09678485 0.11691422 0.12446387 0.13443185 0.14382408 0.14941337 0.15121805] [ 0.05561617 0. 0.02243858 0.04678281 0.07190796 0.09732618 0.10627654 0.11779377 0.12840878 0.13463954 0.13663948] [ 0.06791453 0.02243858 0. 0.033464 0.06421576 0.09178889 0.10123004 0.11326159 0.12426436 0.13069285 0.13275226] [ 0.07991134 0.04678281 0.033464 0. 0.04756675 0.08096499 0.0915302 0.10468255 0.11649841 0.12333236 0.1255126 ] [ 0.09678485 0.07190796 0.06421576 0.04756675 0. 0.05629954 0.07061627 0.08699287 0.10090176 0.10872055 0.11118767] [ 0.11691422 0.09732618 0.09178889 0.08096499 0.05629954 0. 0.02942141 0.05832319 0.07758599 0.08751142 0.09055809] [ 0.12446387 0.10627654 0.10123004 0.0915302 0.07061627 0.02942141 0. 0.03847775 0.06336016 0.075238 0.07876232] [ 0.13443185 0.11779377 0.11326159 0.10468255 0.08699287 0.05832319 0.03847775 0. 0.0326922 0.05006773 0.055258 ] [ 0.14382408 0.12840878 0.12426436 0.11649841 0.10090176 0.07758599 0.06336016 0.0326922 0. 0.02224235 0.03050273] [ 0.14941337 0.13463954 0.13069285 0.12333236 0.10872055 0.08751142 0.075238 0.05006773 0.02224235 0. 0.01078875] [ 0.15121805 0.13663948 0.13275226 0.1255126 0.11118767 0.09055809 0.07876232 0.055258 0.03050273 0.01078875 0. ]] Replica 4 / 40 Computing statistical inefficiencies: lambda 0: g = 1.181 lambda 1: g = 1.080 lambda 2: g = 1.594 lambda 3: g = 1.863 lambda 4: g = 1.364 lambda 5: g = 1.183 lambda 6: g = 1.412 lambda 7: g = 1.829 lambda 8: g = 2.732 lambda 9: g = 1.588 lambda 10: g = 1.878 Subsampling data to produce uncorrelated samples... number of samples per lambda: [494 381 500 416 344 500 457 292 263 266 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.9529 +/- 0.4196, Sum=4.1185 +/- 0.1043 Interval 2, DeltaF=1.8713 +/- 0.2721, Sum=5.2270 +/- 0.1132 Interval 3, DeltaF=3.4974 +/- 0.3080, Sum=7.2986 +/- 0.1263 Interval 4, DeltaF=3.8971 +/- 0.3933, Sum=9.6070 +/- 0.1561 Interval 5, DeltaF=2.3576 +/- 0.4364, Sum=11.0035 +/- 0.1926 Interval 6, DeltaF=-0.4777 +/- 0.3549, Sum=10.7205 +/- 0.2065 Interval 7, DeltaF=-2.1383 +/- 0.5552, Sum=9.4539 +/- 0.2757 Interval 8, DeltaF=-2.3238 +/- 0.3110, Sum=8.0774 +/- 0.2816 Interval 9, DeltaF=-2.8758 +/- 0.2681, Sum=6.3740 +/- 0.2848 Interval 10, DeltaF=-1.1343 +/- 0.1921, Sum=5.7021 +/- 0.2856 Forward EXP free energy: 5.7021 +/- 0.2856 Reverse EXP: Interval 1, DeltaF=6.4601 +/- 0.4607, Sum=3.8266 +/- 0.1257 Interval 2, DeltaF=1.8640 +/- 0.2611, Sum=4.9307 +/- 0.1320 Interval 3, DeltaF=3.3150 +/- 0.3418, Sum=6.8943 +/- 0.1490 Interval 4, DeltaF=3.6477 +/- 0.4395, Sum=9.0549 +/- 0.1879 Interval 5, DeltaF=1.1390 +/- 0.4501, Sum=9.7296 +/- 0.2229 Interval 6, DeltaF=-0.7878 +/- 0.2785, Sum=9.2630 +/- 0.2276 Interval 7, DeltaF=-1.7650 +/- 0.3471, Sum=8.2175 +/- 0.2386 Interval 8, DeltaF=-2.4290 +/- 0.3080, Sum=6.7787 +/- 0.2451 Interval 9, DeltaF=-2.9005 +/- 0.3758, Sum=5.0606 +/- 0.2590 Interval 10, DeltaF=-1.0470 +/- 0.1998, Sum=4.4404 +/- 0.2600 Reverse EXP free energy: 4.4404 +/- 0.2600 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7065 +/- 0.1501, Sum=3.9725 +/- 0.0133 Interval 2, DeltaF=1.8677 +/- 0.0548, Sum=5.0788 +/- 0.0135 Interval 3, DeltaF=3.4062 +/- 0.0819, Sum=7.0964 +/- 0.0140 Interval 4, DeltaF=3.7724 +/- 0.1347, Sum=9.3310 +/- 0.0177 Interval 5, DeltaF=1.7483 +/- 0.1513, Sum=10.3665 +/- 0.0223 Interval 6, DeltaF=-0.6327 +/- 0.0805, Sum=9.9917 +/- 0.0226 Interval 7, DeltaF=-1.9516 +/- 0.1801, Sum=8.8357 +/- 0.0297 Interval 8, DeltaF=-2.3764 +/- 0.0737, Sum=7.4281 +/- 0.0298 Interval 9, DeltaF=-2.8882 +/- 0.0862, Sum=5.7173 +/- 0.0302 Interval 10, DeltaF=-1.0907 +/- 0.0296, Sum=5.0713 +/- 0.0302 Average EXP free energy: 5.0713 +/- 0.0302 Interval 1, DeltaF=6.4601 +/- 0.1633, Sum=3.8266 +/- 0.0158 Interval 2, DeltaF=1.8713 +/- 0.2000, Sum=4.9351 +/- 0.0285 Interval 3, DeltaF=3.3150 +/- 0.2587, Sum=6.8986 +/- 0.0488 Interval 4, DeltaF=3.8971 +/- 0.2609, Sum=9.2070 +/- 0.0633 Interval 5, DeltaF=1.1390 +/- 0.3788, Sum=9.8817 +/- 0.1060 Interval 6, DeltaF=-0.4777 +/- 0.3669, Sum=9.5987 +/- 0.1326 Interval 7, DeltaF=-1.7650 +/- 0.4284, Sum=8.5532 +/- 0.1715 Interval 8, DeltaF=-2.3238 +/- 0.5120, Sum=7.1767 +/- 0.2314 Interval 9, DeltaF=-2.9005 +/- 0.4633, Sum=5.4587 +/- 0.2640 Interval 10, DeltaF=-1.1343 +/- 0.5240, Sum=4.7867 +/- 0.3101 Double-Wide EXP free energy: 4.7867 +/- 0.3101 Method: BAR Interval 1, DeltaF=6.7357 +/- 0.3025, Sum=3.9898 +/- 0.0542 Interval 2, DeltaF=1.9374 +/- 0.2005, Sum=5.1374 +/- 0.0592 Interval 3, DeltaF=3.2418 +/- 0.2544, Sum=7.0576 +/- 0.0705 Interval 4, DeltaF=3.3043 +/- 0.3056, Sum=9.0149 +/- 0.0896 Interval 5, DeltaF=1.2928 +/- 0.3177, Sum=9.7806 +/- 0.1078 Interval 6, DeltaF=-0.6439 +/- 0.2291, Sum=9.3992 +/- 0.1121 Interval 7, DeltaF=-1.8082 +/- 0.2596, Sum=8.3282 +/- 0.1190 Interval 8, DeltaF=-2.3583 +/- 0.2404, Sum=6.9313 +/- 0.1239 Interval 9, DeltaF=-2.9556 +/- 0.2239, Sum=5.1806 +/- 0.1274 Interval 10, DeltaF=-1.0892 +/- 0.1495, Sum=4.5354 +/- 0.1281 BAR free energy: 4.5354 +/- 0.1281 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9139 +/- 0.5002, Sum=4.0953 +/- 0.1482 Interval 2, DeltaF=1.9069 +/- 0.2401, Sum=5.2248 +/- 0.1521 Interval 3, DeltaF=3.2681 +/- 0.3393, Sum=7.1607 +/- 0.1667 Interval 4, DeltaF=3.3664 +/- 0.3872, Sum=9.1547 +/- 0.1889 Interval 5, DeltaF=1.3786 +/- 0.3434, Sum=9.9713 +/- 0.2014 Interval 6, DeltaF=-0.6612 +/- 0.2210, Sum=9.5797 +/- 0.2034 Interval 7, DeltaF=-1.7671 +/- 0.2389, Sum=8.5329 +/- 0.2062 Interval 8, DeltaF=-2.3772 +/- 0.3088, Sum=7.1248 +/- 0.2138 Interval 9, DeltaF=-2.9429 +/- 0.3732, Sum=5.3817 +/- 0.2292 Interval 10, DeltaF=-1.0724 +/- 0.2587, Sum=4.7464 +/- 0.2326 Unopt. BAR free energy: 4.7464 +/- 0.2326 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7398 +/- 0.3022, Sum=3.9923 +/- 0.0541 Interval 2, DeltaF=1.9375 +/- 0.2019, Sum=5.1399 +/- 0.0592 Interval 3, DeltaF=3.2344 +/- 0.2584, Sum=7.0558 +/- 0.0712 Interval 4, DeltaF=3.2969 +/- 0.3137, Sum=9.0087 +/- 0.0920 Interval 5, DeltaF=1.3138 +/- 0.3240, Sum=9.7869 +/- 0.1111 Interval 6, DeltaF=-0.6376 +/- 0.2371, Sum=9.4092 +/- 0.1160 Interval 7, DeltaF=-1.8150 +/- 0.2652, Sum=8.3341 +/- 0.1232 Interval 8, DeltaF=-2.3586 +/- 0.2408, Sum=6.9371 +/- 0.1279 Interval 9, DeltaF=-2.9551 +/- 0.2236, Sum=5.1866 +/- 0.1313 Interval 10, DeltaF=-1.0876 +/- 0.1604, Sum=4.5424 +/- 0.1322 Postopt. BAR free energy: 4.5424 +/- 0.1322 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 875 N_k = [494 381] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.5345082] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.85781837] relative max_delta = 2.724083e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0519 relative max_delta = 3.842475e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7763 relative max_delta = 2.544730e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7357 relative max_delta = 6.032558e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7357 relative max_delta = 1.102153e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7357 relative max_delta = 3.823984e-14 Converged to tolerance of 3.823984e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7357 Final dimensionless free energies f_k = [ 0. 6.73569021] Computing normalized weights... Interval 1, DeltaF=6.7357 +/- 0.3025, Sum=3.9898 +/- 0.0542 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 881 N_k = [381 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.48193495] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82037596] relative max_delta = 1.859182e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8320 relative max_delta = 6.353995e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9369 relative max_delta = 5.414368e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9374 relative max_delta = 2.589276e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9374 relative max_delta = 6.932430e-09 Converged to tolerance of 6.932430e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9374 Final dimensionless free energies f_k = [ 0. 1.93738842] Computing normalized weights... Interval 2, DeltaF=1.9374 +/- 0.2005, Sum=5.1374 +/- 0.0592 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 916 N_k = [500 416] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.58679992] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.40146308] relative max_delta = 3.392362e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4915 relative max_delta = 3.613548e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2881 relative max_delta = 2.422668e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2419 relative max_delta = 1.423762e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2418 relative max_delta = 3.684090e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2418 relative max_delta = 2.527581e-10 Converged to tolerance of 2.527581e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2418 Final dimensionless free energies f_k = [ 0. 3.24181267] Computing normalized weights... Interval 3, DeltaF=3.2418 +/- 0.2544, Sum=7.0576 +/- 0.0705 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 760 N_k = [416 344] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.02452583] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.76412097] relative max_delta = 4.192429e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9455 relative max_delta = 9.321474e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5163 relative max_delta = 4.467322e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3090 relative max_delta = 6.264869e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3043 relative max_delta = 1.439645e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3043 relative max_delta = 7.452065e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3043 relative max_delta = 2.001203e-13 Converged to tolerance of 2.001203e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3043 Final dimensionless free energies f_k = [ 0. 3.30425591] Computing normalized weights... Interval 4, DeltaF=3.3043 +/- 0.3056, Sum=9.0149 +/- 0.0896 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 844 N_k = [344 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.36697972] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.6388301] relative max_delta = 4.255441e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7082 relative max_delta = 9.795442e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3246 relative max_delta = 4.653546e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2929 relative max_delta = 2.453890e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2928 relative max_delta = 7.106696e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2928 relative max_delta = 5.945098e-10 Converged to tolerance of 5.945098e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2928 Final dimensionless free energies f_k = [ 0. 1.29280114] Computing normalized weights... Interval 5, DeltaF=1.2928 +/- 0.3177, Sum=9.7806 +/- 0.1078 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 957 N_k = [500 457] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.40342402] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.55049912] relative max_delta = 2.671668e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5598 relative max_delta = 1.658771e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.6435 relative max_delta = 1.300334e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.6439 relative max_delta = 6.999305e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.6439 relative max_delta = 2.144438e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.6439 relative max_delta = 3.103561e-15 Converged to tolerance of 3.103561e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.6439 Final dimensionless free energies f_k = [ 0. -0.64390606] Computing normalized weights... Interval 6, DeltaF=-0.6439 +/- 0.2291, Sum=9.3992 +/- 0.1121 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 749 N_k = [457 292] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.08918018] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.49831776] relative max_delta = 2.730646e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.5285 relative max_delta = 1.974126e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.8015 relative max_delta = 1.515313e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.8082 relative max_delta = 3.711117e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.8082 relative max_delta = 2.411332e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.8082 relative max_delta = 1.020465e-12 Converged to tolerance of 1.020465e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.8082 Final dimensionless free energies f_k = [ 0. -1.80818613] Computing normalized weights... Interval 7, DeltaF=-1.8082 +/- 0.2596, Sum=8.3282 +/- 0.1190 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 555 N_k = [292 263] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.68481541] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.14592979] relative max_delta = 2.148786e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1672 relative max_delta = 9.799091e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3583 relative max_delta = 8.102845e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3583 relative max_delta = 2.335776e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3583 relative max_delta = 1.577291e-11 Converged to tolerance of 1.577291e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3583 Final dimensionless free energies f_k = [ 0. -2.3583066] Computing normalized weights... Interval 8, DeltaF=-2.3583 +/- 0.2404, Sum=6.9313 +/- 0.1239 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 529 N_k = [263 266] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.25194837] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.7753127] relative max_delta = 1.885785e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7934 relative max_delta = 6.492490e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9564 relative max_delta = 5.512668e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9556 relative max_delta = 2.910990e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9556 relative max_delta = 4.946987e-09 Converged to tolerance of 4.946987e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9556 Final dimensionless free energies f_k = [ 0. -2.95556677] Computing normalized weights... Interval 9, DeltaF=-2.9556 +/- 0.2239, Sum=5.1806 +/- 0.1274 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 766 N_k = [266 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01064269] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08292455] relative max_delta = 6.674690e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0835 relative max_delta = 5.764017e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0892 relative max_delta = 5.159913e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0892 relative max_delta = 3.969853e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0892 relative max_delta = 2.340188e-12 Converged to tolerance of 2.340188e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0892 Final dimensionless free energies f_k = [ 0. -1.0891648] Computing normalized weights... Interval 10, DeltaF=-1.0892 +/- 0.1495, Sum=4.5354 +/- 0.1281 Pairwise MBAR free energy: 4.5354 +/- 0.1281 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4413 N_k = [494 381 500 416 344 500 457 292 263 266 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.99957302 1.99941698 1.77423483 1.45279908 1.61169249 1.60120133 1.49876686 1.33949938 0.80031707 0.4561806 ] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.93547662 3.31482636 3.24337831 2.73982984 2.93595958 2.88054295 2.65048803 2.28183823 1.31808444 0.78805504] relative max_delta = 4.432038e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2004 3.7199 4.1850 4.2647 4.5858 4.4766 4.1263 3.5953 2.4114 1.8168 relative max_delta = 3.597728e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7114 7.5023 12.0780 16.8484 18.2531 17.6556 16.1722 14.0878 10.9176 9.7620 relative max_delta = 7.487658e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6907 8.7275 11.9623 15.7082 16.9630 16.3285 14.5367 12.1846 9.2391 8.1526 relative max_delta = 1.122004e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7089 8.6490 11.8933 15.2031 16.4572 15.8193 14.0207 11.6475 8.7221 7.6337 relative max_delta = 3.263582e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7081 8.6492 11.8884 15.1711 16.4266 15.7887 13.9901 11.6168 8.6915 7.6031 relative max_delta = 1.947460e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7081 8.6492 11.8884 15.1710 16.4265 15.7886 13.9900 11.6167 8.6914 7.6030 relative max_delta = 7.623814e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7081 8.6492 11.8884 15.1710 16.4265 15.7886 13.9900 11.6167 8.6914 7.6030 relative max_delta = 1.166856e-10 Converged to tolerance of 1.166856e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7081 8.6492 11.8884 15.1710 16.4265 15.7886 13.9900 11.6167 8.6914 7.6030 Final dimensionless free energies f_k = [ 0. 6.70814257 8.64922584 11.88835974 15.1710043 16.42651857 15.78860035 13.98999229 11.61668184 8.69135176 7.60299572] Computing normalized weights... DeltaMij: [[ 0. 3.97348336 5.12325947 7.04191945 8.9863524 9.7300404 9.35217761 8.28679489 6.88099448 5.14821223 4.5035383 ] [-3.97348336 0. 1.14977611 3.06843609 5.01286905 5.75655704 5.37869425 4.31331153 2.90751112 1.17472887 0.53005494] [-5.12325947 -1.14977611 0. 1.91865998 3.86309293 4.60678093 4.22891814 3.16353542 1.75773501 0.02495276 -0.61972117] [-7.04191945 -3.06843609 -1.91865998 0. 1.94443296 2.68812095 2.31025816 1.24487544 -0.16092497 -1.89370722 -2.53838115] [-8.9863524 -5.01286905 -3.86309293 -1.94443296 0. 0.74368799 0.36582521 -0.69955751 -2.10535793 -3.83814018 -4.48281411] [-9.7300404 -5.75655704 -4.60678093 -2.68812095 -0.74368799 0. -0.37786279 -1.44324551 -2.84904592 -4.58182817 -5.2265021 ] [-9.35217761 -5.37869425 -4.22891814 -2.31025816 -0.36582521 0.37786279 0. -1.06538272 -2.47118313 -4.20396538 -4.84863931] [-8.28679489 -4.31331153 -3.16353542 -1.24487544 0.69955751 1.44324551 1.06538272 0. -1.40580041 -3.13858266 -3.78325659] [-6.88099448 -2.90751112 -1.75773501 0.16092497 2.10535793 2.84904592 2.47118313 1.40580041 0. -1.73278225 -2.37745618] [-5.14821223 -1.17472887 -0.02495276 1.89370722 3.83814018 4.58182817 4.20396538 3.13858266 1.73278225 0. -0.64467393] [-4.5035383 -0.53005494 0.61972117 2.53838115 4.48281411 5.2265021 4.84863931 3.78325659 2.37745618 0.64467393 0. ]] dDeltaMij: [[ 0. 0.05289879 0.0659957 0.07898916 0.09984268 0.12231096 0.12976119 0.13876888 0.14694226 0.15243385 0.15452459] [ 0.05289879 0. 0.02232977 0.04784801 0.07770727 0.10502552 0.1136149 0.123803 0.1329 0.13894769 0.1412382 ] [ 0.0659957 0.02232977 0. 0.03513972 0.0709197 0.10011004 0.10908712 0.11966134 0.12905062 0.13527052 0.13762224] [ 0.07898916 0.04784801 0.03513972 0. 0.05404524 0.08888121 0.09888367 0.11043916 0.1205489 0.12718525 0.12968367] [ 0.09984268 0.07770727 0.0709197 0.05404524 0. 0.05884311 0.07302759 0.08804772 0.10043697 0.10831269 0.11123582] [ 0.12231096 0.10502552 0.10011004 0.08888121 0.05884311 0. 0.03007743 0.05732468 0.07499795 0.08525461 0.08893872] [ 0.12976119 0.1136149 0.10908712 0.09888367 0.07302759 0.03007743 0. 0.03752191 0.06073034 0.07307195 0.0773401 ] [ 0.13876888 0.123803 0.11966134 0.11043916 0.08804772 0.05732468 0.03752191 0. 0.03123354 0.04943236 0.0555731 ] [ 0.14694226 0.1329 0.12905062 0.1205489 0.10043697 0.07499795 0.06073034 0.03123354 0. 0.02297323 0.03214807] [ 0.15243385 0.13894769 0.13527052 0.12718525 0.10831269 0.08525461 0.07307195 0.04943236 0.02297323 0. 0.01151071] [ 0.15452459 0.1412382 0.13762224 0.12968367 0.11123582 0.08893872 0.0773401 0.0555731 0.03214807 0.01151071 0. ]] Replica 5 / 40 Computing statistical inefficiencies: lambda 0: g = 1.449 lambda 1: g = 3.464 lambda 2: g = 1.649 lambda 3: g = 1.580 lambda 4: g = 1.622 lambda 5: g = 1.891 lambda 6: g = 1.479 lambda 7: g = 1.449 lambda 8: g = 2.488 lambda 9: g = 1.539 lambda 10: g = 2.404 Subsampling data to produce uncorrelated samples... number of samples per lambda: [430 370 456 480 339 500 416 213 255 367 383] Method: EXP Forward EXP: Interval 1, DeltaF=6.8439 +/- 0.4260, Sum=4.0539 +/- 0.1075 Interval 2, DeltaF=2.0298 +/- 0.2849, Sum=5.2562 +/- 0.1178 Interval 3, DeltaF=3.3908 +/- 0.4539, Sum=7.2647 +/- 0.1696 Interval 4, DeltaF=4.1124 +/- 0.4453, Sum=9.7007 +/- 0.2063 Interval 5, DeltaF=1.5341 +/- 0.5853, Sum=10.6094 +/- 0.2894 Interval 6, DeltaF=-0.4720 +/- 0.3951, Sum=10.3298 +/- 0.3038 Interval 7, DeltaF=-1.5170 +/- 0.3601, Sum=9.4312 +/- 0.3134 Interval 8, DeltaF=-2.3761 +/- 0.3285, Sum=8.0238 +/- 0.3198 Interval 9, DeltaF=-2.8684 +/- 0.2669, Sum=6.3247 +/- 0.3226 Interval 10, DeltaF=-1.0801 +/- 0.1819, Sum=5.6849 +/- 0.3232 Forward EXP free energy: 5.6849 +/- 0.3232 Reverse EXP: Interval 1, DeltaF=8.2462 +/- 0.9172, Sum=4.8845 +/- 0.4983 Interval 2, DeltaF=1.8992 +/- 0.2873, Sum=6.0095 +/- 0.5007 Interval 3, DeltaF=3.2293 +/- 0.3276, Sum=7.9224 +/- 0.5047 Interval 4, DeltaF=3.1787 +/- 0.4027, Sum=9.8052 +/- 0.5137 Interval 5, DeltaF=1.3379 +/- 0.4065, Sum=10.5977 +/- 0.5230 Interval 6, DeltaF=-0.4863 +/- 0.2938, Sum=10.3097 +/- 0.5255 Interval 7, DeltaF=-1.6671 +/- 0.3803, Sum=9.3222 +/- 0.5324 Interval 8, DeltaF=-2.3144 +/- 0.3499, Sum=7.9513 +/- 0.5373 Interval 9, DeltaF=-2.8460 +/- 0.3023, Sum=6.2655 +/- 0.5400 Interval 10, DeltaF=-1.0355 +/- 0.1970, Sum=5.6521 +/- 0.5405 Reverse EXP free energy: 5.6521 +/- 0.5405 Averge of forward and reverse EXP: Interval 1, DeltaF=7.5451 +/- 0.4683, Sum=4.4692 +/- 0.1299 Interval 2, DeltaF=1.9645 +/- 0.0630, Sum=5.6329 +/- 0.1299 Interval 3, DeltaF=3.3100 +/- 0.1264, Sum=7.5935 +/- 0.1303 Interval 4, DeltaF=3.6456 +/- 0.1394, Sum=9.7530 +/- 0.1308 Interval 5, DeltaF=1.4360 +/- 0.2070, Sum=10.6036 +/- 0.1332 Interval 6, DeltaF=-0.4791 +/- 0.0971, Sum=10.3198 +/- 0.1333 Interval 7, DeltaF=-1.5921 +/- 0.1057, Sum=9.3767 +/- 0.1335 Interval 8, DeltaF=-2.3453 +/- 0.0888, Sum=7.9875 +/- 0.1336 Interval 9, DeltaF=-2.8572 +/- 0.0631, Sum=6.2951 +/- 0.1336 Interval 10, DeltaF=-1.0578 +/- 0.0278, Sum=5.6685 +/- 0.1336 Average EXP free energy: 5.6685 +/- 0.1336 Interval 1, DeltaF=8.2462 +/- 0.6474, Sum=4.8845 +/- 0.2483 Interval 2, DeltaF=2.0298 +/- 0.2072, Sum=6.0868 +/- 0.2496 Interval 3, DeltaF=3.2293 +/- 0.9237, Sum=7.9997 +/- 0.5636 Interval 4, DeltaF=4.1124 +/- 0.3470, Sum=10.4356 +/- 0.5681 Interval 5, DeltaF=1.3379 +/- 0.9525, Sum=11.2281 +/- 0.7821 Interval 6, DeltaF=-0.4720 +/- 0.5452, Sum=10.9486 +/- 0.8016 Interval 7, DeltaF=-1.6671 +/- 0.9720, Sum=9.9611 +/- 0.9776 Interval 8, DeltaF=-2.3761 +/- 0.5817, Sum=8.5536 +/- 0.9980 Interval 9, DeltaF=-2.8460 +/- 0.9899, Sum=6.8678 +/- 1.1545 Interval 10, DeltaF=-1.0801 +/- 0.5933, Sum=6.2280 +/- 1.1731 Double-Wide EXP free energy: 6.2280 +/- 1.1731 Method: BAR Interval 1, DeltaF=6.7893 +/- 0.3083, Sum=4.0216 +/- 0.0563 Interval 2, DeltaF=1.9859 +/- 0.2027, Sum=5.1979 +/- 0.0614 Interval 3, DeltaF=3.2743 +/- 0.2467, Sum=7.1373 +/- 0.0712 Interval 4, DeltaF=3.3925 +/- 0.2981, Sum=9.1468 +/- 0.0885 Interval 5, DeltaF=1.3506 +/- 0.3099, Sum=9.9468 +/- 0.1052 Interval 6, DeltaF=-0.5617 +/- 0.2301, Sum=9.6141 +/- 0.1098 Interval 7, DeltaF=-1.7140 +/- 0.2737, Sum=8.5988 +/- 0.1184 Interval 8, DeltaF=-2.3579 +/- 0.2535, Sum=7.2021 +/- 0.1244 Interval 9, DeltaF=-2.8851 +/- 0.2161, Sum=5.4932 +/- 0.1274 Interval 10, DeltaF=-1.0643 +/- 0.1535, Sum=4.8627 +/- 0.1282 BAR free energy: 4.8627 +/- 0.1282 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8145 +/- 0.5204, Sum=4.0365 +/- 0.1604 Interval 2, DeltaF=2.0229 +/- 0.2517, Sum=5.2347 +/- 0.1647 Interval 3, DeltaF=3.3307 +/- 0.3215, Sum=7.2076 +/- 0.1757 Interval 4, DeltaF=3.5697 +/- 0.4085, Sum=9.3220 +/- 0.2016 Interval 5, DeltaF=1.3038 +/- 0.3416, Sum=10.0943 +/- 0.2131 Interval 6, DeltaF=-0.5553 +/- 0.2210, Sum=9.7653 +/- 0.2151 Interval 7, DeltaF=-1.6979 +/- 0.2351, Sum=8.7596 +/- 0.2176 Interval 8, DeltaF=-2.3337 +/- 0.3489, Sum=7.3773 +/- 0.2292 Interval 9, DeltaF=-2.8485 +/- 0.3919, Sum=5.6900 +/- 0.2466 Interval 10, DeltaF=-1.0518 +/- 0.2143, Sum=5.0669 +/- 0.2481 Unopt. BAR free energy: 5.0669 +/- 0.2481 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7937 +/- 0.3086, Sum=4.0242 +/- 0.0564 Interval 2, DeltaF=1.9855 +/- 0.2030, Sum=5.2003 +/- 0.0615 Interval 3, DeltaF=3.2762 +/- 0.2488, Sum=7.1409 +/- 0.0716 Interval 4, DeltaF=3.4224 +/- 0.3131, Sum=9.1681 +/- 0.0922 Interval 5, DeltaF=1.3431 +/- 0.3179, Sum=9.9636 +/- 0.1099 Interval 6, DeltaF=-0.5636 +/- 0.2415, Sum=9.6298 +/- 0.1152 Interval 7, DeltaF=-1.7141 +/- 0.2848, Sum=8.6145 +/- 0.1248 Interval 8, DeltaF=-2.3532 +/- 0.2593, Sum=7.2206 +/- 0.1310 Interval 9, DeltaF=-2.8871 +/- 0.2127, Sum=5.5105 +/- 0.1337 Interval 10, DeltaF=-1.0636 +/- 0.1545, Sum=4.8805 +/- 0.1345 Postopt. BAR free energy: 4.8805 +/- 0.1345 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 800 N_k = [430 370] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.74086366] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 5.01093575] relative max_delta = 2.534601e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1896 relative max_delta = 3.443516e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7885 relative max_delta = 2.355293e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7893 relative max_delta = 1.121212e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7893 relative max_delta = 5.801000e-10 Converged to tolerance of 5.801000e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7893 Final dimensionless free energies f_k = [ 0. 6.78930371] Computing normalized weights... Interval 1, DeltaF=6.7893 +/- 0.3083, Sum=4.0216 +/- 0.0563 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 826 N_k = [370 456] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53601472] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.87204399] relative max_delta = 1.794986e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8834 relative max_delta = 6.017886e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9855 relative max_delta = 5.141756e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9859 relative max_delta = 2.021738e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9859 relative max_delta = 3.750801e-09 Converged to tolerance of 3.750801e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9859 Final dimensionless free energies f_k = [ 0. 1.98586725] Computing normalized weights... Interval 2, DeltaF=1.9859 +/- 0.2027, Sum=5.1979 +/- 0.0614 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 936 N_k = [456 480] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.70202073] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.52016989] relative max_delta = 3.246405e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5983 relative max_delta = 3.008002e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2952 relative max_delta = 2.114694e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2743 relative max_delta = 6.375109e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2743 relative max_delta = 2.807084e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2743 relative max_delta = 5.650349e-13 Converged to tolerance of 5.650349e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2743 Final dimensionless free energies f_k = [ 0. 3.27426816] Computing normalized weights... Interval 3, DeltaF=3.2743 +/- 0.2467, Sum=7.1373 +/- 0.0712 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 819 N_k = [480 339] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.95083765] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.6843002] relative max_delta = 4.354702e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9107 relative max_delta = 1.184899e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8080 relative max_delta = 4.982459e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4162 relative max_delta = 1.146917e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3926 relative max_delta = 6.973802e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3925 relative max_delta = 2.538618e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3925 relative max_delta = 3.358487e-10 Converged to tolerance of 3.358487e-10 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3925 Final dimensionless free energies f_k = [ 0. 3.3924804] Computing normalized weights... Interval 4, DeltaF=3.3925 +/- 0.2981, Sum=9.1468 +/- 0.0885 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 839 N_k = [339 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.40352584] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.69904667] relative max_delta = 4.227484e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7686 relative max_delta = 9.052457e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3856 relative max_delta = 4.452594e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3507 relative max_delta = 2.582733e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3506 relative max_delta = 8.300945e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3506 relative max_delta = 8.595981e-10 Converged to tolerance of 8.595981e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3506 Final dimensionless free energies f_k = [ 0. 1.35056316] Computing normalized weights... Interval 5, DeltaF=1.3506 +/- 0.3099, Sum=9.9468 +/- 0.1052 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 916 N_k = [500 416] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.3533093] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.48201104] relative max_delta = 2.670099e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4899 relative max_delta = 1.617757e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5614 relative max_delta = 1.272241e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5617 relative max_delta = 6.624678e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5617 relative max_delta = 1.876223e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5617 relative max_delta = 1.383512e-15 Converged to tolerance of 1.383512e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5617 Final dimensionless free energies f_k = [ 0. -0.56172705] Computing normalized weights... Interval 6, DeltaF=-0.5617 +/- 0.2301, Sum=9.6141 +/- 0.1098 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 629 N_k = [416 213] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.02348865] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.41820813] relative max_delta = 2.783227e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4468 relative max_delta = 1.979429e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7063 relative max_delta = 1.520315e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7140 relative max_delta = 4.540456e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7140 relative max_delta = 4.264580e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7140 relative max_delta = 3.766247e-12 Converged to tolerance of 3.766247e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7140 Final dimensionless free energies f_k = [ 0. -1.71404119] Computing normalized weights... Interval 7, DeltaF=-1.7140 +/- 0.2737, Sum=8.5988 +/- 0.1184 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 468 N_k = [213 255] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.69135717] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.14491081] relative max_delta = 2.114557e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1664 relative max_delta = 9.913683e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3593 relative max_delta = 8.176564e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3579 relative max_delta = 5.888441e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3579 relative max_delta = 2.239024e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3579 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3579 Final dimensionless free energies f_k = [ 0. -2.35790863] Computing normalized weights... Interval 8, DeltaF=-2.3579 +/- 0.2535, Sum=7.2021 +/- 0.1244 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 622 N_k = [255 367] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.25769243] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.72997109] relative max_delta = 1.729977e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7457 relative max_delta = 5.725320e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8868 relative max_delta = 4.886466e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8851 relative max_delta = 5.661680e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8851 relative max_delta = 6.732130e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8851 relative max_delta = 1.385317e-15 Converged to tolerance of 1.385317e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8851 Final dimensionless free energies f_k = [ 0. -2.8851175] Computing normalized weights... Interval 9, DeltaF=-2.8851 +/- 0.2161, Sum=5.4932 +/- 0.1274 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 750 N_k = [367 383] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96594626] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.05500415] relative max_delta = 8.441473e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0559 relative max_delta = 8.815203e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0643 relative max_delta = 7.871007e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0643 relative max_delta = 9.372311e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0643 relative max_delta = 1.439530e-14 Converged to tolerance of 1.439530e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0643 Final dimensionless free energies f_k = [ 0. -1.06431119] Computing normalized weights... Interval 10, DeltaF=-1.0643 +/- 0.1535, Sum=4.8627 +/- 0.1282 Pairwise MBAR free energy: 4.8627 +/- 0.1282 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4209 N_k = [430 370 456 480 339 500 416 213 255 367 383] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.97657579 2.00551886 1.95739748 1.46711759 1.68081017 1.66557183 1.62110244 1.53093214 0.92527762 0.48709576] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.91004822 3.32721998 3.52458468 2.77029606 3.04966563 3.00941305 2.86333804 2.57255115 1.51058535 0.88839942] relative max_delta = 4.446445e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1626 3.7137 4.3819 4.2956 4.7005 4.6146 4.3583 3.9048 2.6340 1.9620 relative max_delta = 3.512080e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5852 7.3533 11.6794 17.1202 18.6226 18.1190 16.8079 14.7873 11.6517 10.5432 relative max_delta = 7.475907e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7182 8.7951 12.0527 16.0697 17.4434 16.8942 15.1930 12.8904 9.9964 8.9210 relative max_delta = 1.087499e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7611 8.7303 12.0100 15.4507 16.8267 16.2722 14.5569 12.2325 9.3578 8.2816 relative max_delta = 3.909726e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7598 8.7307 12.0011 15.3828 16.7611 16.2067 14.4913 12.1668 9.2922 8.2160 relative max_delta = 4.054944e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7598 8.7306 12.0011 15.3821 16.7604 16.2060 14.4907 12.1661 9.2916 8.2153 relative max_delta = 4.243876e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7598 8.7306 12.0011 15.3821 16.7604 16.2060 14.4907 12.1661 9.2916 8.2153 relative max_delta = 4.812351e-09 Converged to tolerance of 4.812351e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7598 8.7306 12.0011 15.3821 16.7604 16.2060 14.4907 12.1661 9.2916 8.2153 Final dimensionless free energies f_k = [ 0. 6.75978535 8.73064562 12.00108284 15.38205035 16.76044623 16.20598317 14.49066521 12.16610329 9.29156737 8.21531136] Computing normalized weights... DeltaMij: [[ 0. 4.00407331 5.17148745 7.10868955 9.11136287 9.92783822 9.59940904 8.58336216 7.20643732 5.50374235 4.86623572] [-4.00407331 0. 1.16741414 3.10461624 5.10728956 5.92376492 5.59533574 4.57928885 3.20236401 1.49966904 0.86216241] [-5.17148745 -1.16741414 0. 1.9372021 3.93987542 4.75635078 4.4279216 3.41187471 2.03494987 0.3322549 -0.30525173] [-7.10868955 -3.10461624 -1.9372021 0. 2.00267332 2.81914868 2.4907195 1.47467261 0.09774777 -1.6049472 -2.24245383] [-9.11136287 -5.10728956 -3.93987542 -2.00267332 0. 0.81647535 0.48804618 -0.52800071 -1.90492555 -3.60762052 -4.24512715] [-9.92783822 -5.92376492 -4.75635078 -2.81914868 -0.81647535 0. -0.32842918 -1.34447606 -2.7214009 -4.42409587 -5.0616025 ] [-9.59940904 -5.59533574 -4.4279216 -2.4907195 -0.48804618 0.32842918 0. -1.01604689 -2.39297172 -4.09566669 -4.73317333] [-8.58336216 -4.57928885 -3.41187471 -1.47467261 0.52800071 1.34447606 1.01604689 0. -1.37692484 -3.07961981 -3.71712644] [-7.20643732 -3.20236401 -2.03494987 -0.09774777 1.90492555 2.7214009 2.39297172 1.37692484 0. -1.70269497 -2.3402016 ] [-5.50374235 -1.49966904 -0.3322549 1.6049472 3.60762052 4.42409587 4.09566669 3.07961981 1.70269497 0. -0.63750663] [-4.86623572 -0.86216241 0.30525173 2.24245383 4.24512715 5.0616025 4.73317333 3.71712644 2.3402016 0.63750663 0. ]] dDeltaMij: [[ 0. 0.05558772 0.06886686 0.0810494 0.09929921 0.12004413 0.12763936 0.13828195 0.1480912 0.15387068 0.15602878] [ 0.05558772 0. 0.02281499 0.04726437 0.07435052 0.10039077 0.10935958 0.12161254 0.13266015 0.13908235 0.14146622] [ 0.06886686 0.02281499 0. 0.03395592 0.06692077 0.09501995 0.10445095 0.11721814 0.12864369 0.13525672 0.13770685] [ 0.0810494 0.04726437 0.03395592 0. 0.0509437 0.08446561 0.09495148 0.10883871 0.12105773 0.12806309 0.13064819] [ 0.09929921 0.07435052 0.06692077 0.0509437 0. 0.05455873 0.06963892 0.08763729 0.10241748 0.1106098 0.11359279] [ 0.12004413 0.10039077 0.09501995 0.08446561 0.05455873 0. 0.03022869 0.06086161 0.08073126 0.09089749 0.09450463] [ 0.12763936 0.10935958 0.10445095 0.09495148 0.06963892 0.03022869 0. 0.04139193 0.06670875 0.07875589 0.08289455] [ 0.13828195 0.12161254 0.11721814 0.10883871 0.08763729 0.06086161 0.04139193 0. 0.03350357 0.0514633 0.05763006] [ 0.1480912 0.13266015 0.12864369 0.12105773 0.10241748 0.08073126 0.06670875 0.03350357 0. 0.0231361 0.03281289] [ 0.15387068 0.13908235 0.13525672 0.12806309 0.1106098 0.09089749 0.07875589 0.0514633 0.0231361 0. 0.01236576] [ 0.15602878 0.14146622 0.13770685 0.13064819 0.11359279 0.09450463 0.08289455 0.05763006 0.03281289 0.01236576 0. ]] Replica 6 / 40 Computing statistical inefficiencies: lambda 0: g = 2.965 lambda 1: g = 3.190 lambda 2: g = 1.657 lambda 3: g = 2.115 lambda 4: g = 2.078 lambda 5: g = 1.848 lambda 6: g = 1.000 lambda 7: g = 2.519 lambda 8: g = 2.013 lambda 9: g = 1.616 lambda 10: g = 2.767 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 500 380 400 247 266 241 323 323 373] Method: EXP Forward EXP: Interval 1, DeltaF=6.9660 +/- 0.4694, Sum=4.1262 +/- 0.1305 Interval 2, DeltaF=1.8165 +/- 0.2618, Sum=5.2022 +/- 0.1367 Interval 3, DeltaF=3.0610 +/- 0.3619, Sum=7.0154 +/- 0.1572 Interval 4, DeltaF=4.2049 +/- 0.3521, Sum=9.5061 +/- 0.1735 Interval 5, DeltaF=2.2958 +/- 0.3691, Sum=10.8660 +/- 0.1913 Interval 6, DeltaF=-0.8780 +/- 0.6042, Sum=10.3459 +/- 0.2887 Interval 7, DeltaF=-1.6013 +/- 0.4228, Sum=9.3974 +/- 0.3075 Interval 8, DeltaF=-2.7085 +/- 0.4231, Sum=7.7930 +/- 0.3253 Interval 9, DeltaF=-2.9527 +/- 0.2851, Sum=6.0440 +/- 0.3288 Interval 10, DeltaF=-1.0877 +/- 0.1846, Sum=5.3997 +/- 0.3295 Forward EXP free energy: 5.3997 +/- 0.3295 Reverse EXP: Interval 1, DeltaF=6.5864 +/- 0.5931, Sum=3.9014 +/- 0.2084 Interval 2, DeltaF=2.0186 +/- 0.2897, Sum=5.0971 +/- 0.2142 Interval 3, DeltaF=2.9420 +/- 0.3478, Sum=6.8397 +/- 0.2259 Interval 4, DeltaF=3.4494 +/- 0.4003, Sum=8.8829 +/- 0.2450 Interval 5, DeltaF=1.3997 +/- 0.4765, Sum=9.7120 +/- 0.2795 Interval 6, DeltaF=-0.5937 +/- 0.3148, Sum=9.3603 +/- 0.2856 Interval 7, DeltaF=-1.7594 +/- 0.3347, Sum=8.3182 +/- 0.2932 Interval 8, DeltaF=-2.1540 +/- 0.3413, Sum=7.0423 +/- 0.3012 Interval 9, DeltaF=-2.8964 +/- 0.2982, Sum=5.3266 +/- 0.3058 Interval 10, DeltaF=-1.0627 +/- 0.1999, Sum=4.6971 +/- 0.3067 Reverse EXP free energy: 4.6971 +/- 0.3067 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7762 +/- 0.2259, Sum=4.0138 +/- 0.0302 Interval 2, DeltaF=1.9176 +/- 0.0590, Sum=5.1496 +/- 0.0303 Interval 3, DeltaF=3.0015 +/- 0.0970, Sum=6.9276 +/- 0.0308 Interval 4, DeltaF=3.8271 +/- 0.1102, Sum=9.1945 +/- 0.0316 Interval 5, DeltaF=1.8477 +/- 0.1441, Sum=10.2890 +/- 0.0339 Interval 6, DeltaF=-0.7358 +/- 0.2059, Sum=9.8531 +/- 0.0422 Interval 7, DeltaF=-1.6804 +/- 0.1148, Sum=8.8578 +/- 0.0429 Interval 8, DeltaF=-2.4313 +/- 0.1162, Sum=7.4176 +/- 0.0437 Interval 9, DeltaF=-2.9246 +/- 0.0656, Sum=5.6853 +/- 0.0437 Interval 10, DeltaF=-1.0752 +/- 0.0286, Sum=5.0484 +/- 0.0438 Average EXP free energy: 5.0484 +/- 0.0438 Interval 1, DeltaF=6.5864 +/- 0.2708, Sum=3.9014 +/- 0.0434 Interval 2, DeltaF=1.8165 +/- 0.2456, Sum=4.9774 +/- 0.0562 Interval 3, DeltaF=2.9420 +/- 0.4045, Sum=6.7200 +/- 0.1121 Interval 4, DeltaF=4.2049 +/- 0.3042, Sum=9.2108 +/- 0.1247 Interval 5, DeltaF=1.3997 +/- 0.4830, Sum=10.0398 +/- 0.1862 Interval 6, DeltaF=-0.8780 +/- 0.4500, Sum=9.5198 +/- 0.2215 Interval 7, DeltaF=-1.7594 +/- 0.5319, Sum=8.4776 +/- 0.2777 Interval 8, DeltaF=-2.7085 +/- 0.5817, Sum=6.8733 +/- 0.3425 Interval 9, DeltaF=-2.8964 +/- 0.5577, Sum=5.1576 +/- 0.3889 Interval 10, DeltaF=-1.0877 +/- 0.6048, Sum=4.5134 +/- 0.4452 Double-Wide EXP free energy: 4.5134 +/- 0.4452 Method: BAR Interval 1, DeltaF=6.7824 +/- 0.2912, Sum=4.0174 +/- 0.0502 Interval 2, DeltaF=1.9321 +/- 0.1979, Sum=5.1619 +/- 0.0553 Interval 3, DeltaF=3.1046 +/- 0.2568, Sum=7.0009 +/- 0.0677 Interval 4, DeltaF=3.3359 +/- 0.3008, Sum=8.9768 +/- 0.0864 Interval 5, DeltaF=1.3101 +/- 0.3472, Sum=9.7529 +/- 0.1121 Interval 6, DeltaF=-0.5511 +/- 0.2610, Sum=9.4265 +/- 0.1191 Interval 7, DeltaF=-1.6738 +/- 0.2827, Sum=8.4350 +/- 0.1282 Interval 8, DeltaF=-2.3030 +/- 0.2442, Sum=7.0709 +/- 0.1330 Interval 9, DeltaF=-2.8846 +/- 0.2166, Sum=5.3622 +/- 0.1358 Interval 10, DeltaF=-1.0766 +/- 0.1515, Sum=4.7245 +/- 0.1365 BAR free energy: 4.7245 +/- 0.1365 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9221 +/- 0.4440, Sum=4.1002 +/- 0.1168 Interval 2, DeltaF=1.8645 +/- 0.2536, Sum=5.2046 +/- 0.1228 Interval 3, DeltaF=2.9896 +/- 0.3446, Sum=6.9755 +/- 0.1415 Interval 4, DeltaF=3.5102 +/- 0.3872, Sum=9.0547 +/- 0.1671 Interval 5, DeltaF=1.3318 +/- 0.3982, Sum=9.8435 +/- 0.1917 Interval 6, DeltaF=-0.5519 +/- 0.2579, Sum=9.5166 +/- 0.1957 Interval 7, DeltaF=-1.6666 +/- 0.2817, Sum=8.5294 +/- 0.2012 Interval 8, DeltaF=-2.2144 +/- 0.3384, Sum=7.2177 +/- 0.2124 Interval 9, DeltaF=-2.8735 +/- 0.3484, Sum=5.5156 +/- 0.2242 Interval 10, DeltaF=-1.0721 +/- 0.2270, Sum=4.8806 +/- 0.2263 Unopt. BAR free energy: 4.8806 +/- 0.2263 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7753 +/- 0.2925, Sum=4.0133 +/- 0.0507 Interval 2, DeltaF=1.9340 +/- 0.1982, Sum=5.1589 +/- 0.0558 Interval 3, DeltaF=3.1018 +/- 0.2581, Sum=6.9961 +/- 0.0683 Interval 4, DeltaF=3.3403 +/- 0.3099, Sum=8.9747 +/- 0.0889 Interval 5, DeltaF=1.3102 +/- 0.3597, Sum=9.7508 +/- 0.1174 Interval 6, DeltaF=-0.5531 +/- 0.2701, Sum=9.4232 +/- 0.1251 Interval 7, DeltaF=-1.6798 +/- 0.2899, Sum=8.4282 +/- 0.1346 Interval 8, DeltaF=-2.2882 +/- 0.2498, Sum=7.0728 +/- 0.1396 Interval 9, DeltaF=-2.8858 +/- 0.2161, Sum=5.3634 +/- 0.1423 Interval 10, DeltaF=-1.0763 +/- 0.1545, Sum=4.7259 +/- 0.1430 Postopt. BAR free energy: 4.7259 +/- 0.1430 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.38682279] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.77068018] relative max_delta = 2.900755e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9752 relative max_delta = 4.111429e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7962 relative max_delta = 2.679350e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7823 relative max_delta = 2.037306e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7824 relative max_delta = 6.872301e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7824 relative max_delta = 7.896549e-14 Converged to tolerance of 7.896549e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7824 Final dimensionless free energies f_k = [ 0. 6.78235014] Computing normalized weights... Interval 1, DeltaF=6.7824 +/- 0.2912, Sum=4.0174 +/- 0.0502 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.45639316] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.80212121] relative max_delta = 1.918451e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8151 relative max_delta = 7.162632e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9321 relative max_delta = 6.055182e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9321 relative max_delta = 1.233432e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9321 relative max_delta = 2.861588e-14 Converged to tolerance of 2.861588e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9321 Final dimensionless free energies f_k = [ 0. 1.93211298] Computing normalized weights... Interval 2, DeltaF=1.9321 +/- 0.1979, Sum=5.1619 +/- 0.0553 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 880 N_k = [500 380] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.62036522] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.38520526] relative max_delta = 3.206601e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4607 relative max_delta = 3.066145e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1316 relative max_delta = 2.142479e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1046 relative max_delta = 8.680130e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1046 relative max_delta = 9.953293e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1046 relative max_delta = 1.332650e-11 Converged to tolerance of 1.332650e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1046 Final dimensionless free energies f_k = [ 0. 3.10460906] Computing normalized weights... Interval 3, DeltaF=3.1046 +/- 0.2568, Sum=7.0009 +/- 0.0677 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 780 N_k = [380 400] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.96498951] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.69775902] relative max_delta = 4.316098e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8957 relative max_delta = 1.044215e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5976 relative max_delta = 4.730626e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3429 relative max_delta = 7.619280e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3359 relative max_delta = 2.102726e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3359 relative max_delta = 1.609574e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3359 relative max_delta = 9.450550e-13 Converged to tolerance of 9.450550e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3359 Final dimensionless free energies f_k = [ 0. 3.33587931] Computing normalized weights... Interval 4, DeltaF=3.3359 +/- 0.3008, Sum=8.9768 +/- 0.0864 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 647 N_k = [400 247] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.35010869] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.61645786] relative max_delta = 4.320639e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6941 relative max_delta = 1.118552e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3750 relative max_delta = 4.952115e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3108 relative max_delta = 4.899705e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3101 relative max_delta = 5.119206e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3101 relative max_delta = 5.516775e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3101 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3101 Final dimensionless free energies f_k = [ 0. 1.31012775] Computing normalized weights... Interval 5, DeltaF=1.3101 +/- 0.3472, Sum=9.7529 +/- 0.1121 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 513 N_k = [247 266] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.35639637] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.47979331] relative max_delta = 2.571877e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4869 relative max_delta = 1.459941e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5509 relative max_delta = 1.161896e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5511 relative max_delta = 2.801311e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5511 relative max_delta = 1.785741e-09 Converged to tolerance of 1.785741e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5511 Final dimensionless free energies f_k = [ 0. -0.55106644] Computing normalized weights... Interval 6, DeltaF=-0.5511 +/- 0.2610, Sum=9.4265 +/- 0.1191 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 507 N_k = [266 241] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.02418231] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.39627437] relative max_delta = 2.664892e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4236 relative max_delta = 1.921540e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6705 relative max_delta = 1.477859e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6738 relative max_delta = 1.974890e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6738 relative max_delta = 4.082753e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6738 relative max_delta = 1.817413e-14 Converged to tolerance of 1.817413e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6738 Final dimensionless free energies f_k = [ 0. -1.67381369] Computing normalized weights... Interval 7, DeltaF=-1.6738 +/- 0.2827, Sum=8.4350 +/- 0.1282 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 564 N_k = [241 323] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.66102227] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.09627398] relative max_delta = 2.076311e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1172 relative max_delta = 9.865045e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3047 relative max_delta = 8.136577e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3030 relative max_delta = 7.332487e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3030 relative max_delta = 4.781444e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3030 relative max_delta = 1.928313e-16 Converged to tolerance of 1.928313e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3030 Final dimensionless free energies f_k = [ 0. -2.30299332] Computing normalized weights... Interval 8, DeltaF=-2.3030 +/- 0.2442, Sum=7.0709 +/- 0.1330 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 646 N_k = [323 323] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.15477775] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.68878343] relative max_delta = 1.986049e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7085 relative max_delta = 7.274743e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8855 relative max_delta = 6.135918e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8846 relative max_delta = 3.246148e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8846 relative max_delta = 5.154927e-09 Converged to tolerance of 5.154927e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8846 Final dimensionless free energies f_k = [ 0. -2.88460504] Computing normalized weights... Interval 9, DeltaF=-2.8846 +/- 0.2166, Sum=5.3622 +/- 0.1358 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 696 N_k = [323 373] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98837425] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06920782] relative max_delta = 7.560137e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0699 relative max_delta = 6.918641e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0766 relative max_delta = 6.187885e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0766 relative max_delta = 1.516703e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0766 relative max_delta = 8.992262e-14 Converged to tolerance of 8.992262e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0766 Final dimensionless free energies f_k = [ 0. -1.07660838] Computing normalized weights... Interval 10, DeltaF=-1.0766 +/- 0.1515, Sum=4.7245 +/- 0.1365 Pairwise MBAR free energy: 4.7245 +/- 0.1365 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4053 N_k = [500 500 500 380 400 247 266 241 323 323 373] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.05622629 2.04285056 1.78882126 1.52937616 1.78798835 1.8189579 1.79581207 1.6359331 0.85804432 0.39422462] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.07191782 3.43491074 3.29274554 2.87455618 3.2683473 3.29274897 3.15597429 2.72384614 1.40046228 0.73263217] relative max_delta = 4.378350e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3536 3.8617 4.2662 4.4521 4.9531 4.9230 4.6638 4.0536 2.5440 1.8313 relative max_delta = 3.401442e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.0093 7.8378 12.3598 17.4332 18.8554 18.3342 16.9323 14.6794 11.5408 10.4334 relative max_delta = 7.373107e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7936 8.8626 11.9603 15.8879 17.1693 16.6182 14.9837 12.6976 9.7808 8.6875 relative max_delta = 1.154297e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8023 8.7424 11.8365 15.2036 16.4825 15.9291 14.2918 12.0028 9.0908 7.9984 relative max_delta = 4.215459e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8012 8.7428 11.8256 15.1439 16.4240 15.8706 14.2334 11.9443 9.0323 7.9400 relative max_delta = 3.636574e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8013 8.7428 11.8255 15.1434 16.4236 15.8702 14.2330 11.9439 9.0319 7.9395 relative max_delta = 2.763543e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8013 8.7428 11.8255 15.1434 16.4236 15.8702 14.2330 11.9439 9.0319 7.9395 relative max_delta = 1.626489e-09 Converged to tolerance of 1.626489e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8013 8.7428 11.8255 15.1434 16.4236 15.8702 14.2330 11.9439 9.0319 7.9395 Final dimensionless free energies f_k = [ 0. 6.80125023 8.7427809 11.82548449 15.14342125 16.42360095 15.87018871 14.23295825 11.94388371 9.03190446 7.93952964] Computing normalized weights... DeltaMij: [[ 0. 4.0286345 5.17867562 7.00467608 8.97001394 9.72831218 9.40050544 8.4307127 7.07480837 5.34993431 4.70287991] [-4.0286345 0. 1.15004112 2.97604158 4.94137943 5.69967768 5.37187094 4.4020782 3.04617386 1.3212998 0.67424541] [-5.17867562 -1.15004112 0. 1.82600046 3.79133831 4.54963656 4.22182982 3.25203708 1.89613274 0.17125868 -0.47579572] [-7.00467608 -2.97604158 -1.82600046 0. 1.96533785 2.7236361 2.39582936 1.42603662 0.07013228 -1.65474178 -2.30179617] [-8.97001394 -4.94137943 -3.79133831 -1.96533785 0. 0.75829824 0.4304915 -0.53930124 -1.89520557 -3.62007963 -4.26713403] [-9.72831218 -5.69967768 -4.54963656 -2.7236361 -0.75829824 0. -0.32780674 -1.29759948 -2.65350381 -4.37837787 -5.02543227] [-9.40050544 -5.37187094 -4.22182982 -2.39582936 -0.4304915 0.32780674 0. -0.96979274 -2.32569708 -4.05057114 -4.69762553] [-8.4307127 -4.4020782 -3.25203708 -1.42603662 0.53930124 1.29759948 0.96979274 0. -1.35590433 -3.08077839 -3.72783279] [-7.07480837 -3.04617386 -1.89613274 -0.07013228 1.89520557 2.65350381 2.32569708 1.35590433 0. -1.72487406 -2.37192846] [-5.34993431 -1.3212998 -0.17125868 1.65474178 3.62007963 4.37837787 4.05057114 3.08077839 1.72487406 0. -0.6470544 ] [-4.70287991 -0.67424541 0.47579572 2.30179617 4.26713403 5.02543227 4.69762553 3.72783279 2.37192846 0.6470544 0. ]] dDeltaMij: [[ 0. 0.04888917 0.06142598 0.0751681 0.0957816 0.12389735 0.13640413 0.14858429 0.15726122 0.16231168 0.1642542 ] [ 0.04888917 0. 0.02210675 0.04784914 0.07630398 0.1095399 0.12350919 0.13684198 0.14621739 0.15163613 0.15371362] [ 0.06142598 0.02210675 0. 0.03514996 0.06930673 0.10478748 0.11931446 0.13306821 0.14269179 0.14823946 0.15036389] [ 0.0751681 0.04784914 0.03514996 0. 0.05210114 0.09424788 0.11017442 0.12493836 0.13514213 0.14098718 0.14321922] [ 0.0957816 0.07630398 0.06930673 0.05210114 0. 0.06864155 0.08921032 0.10691273 0.11867642 0.125292 0.12779847] [ 0.12389735 0.1095399 0.10478748 0.09424788 0.06864155 0. 0.03812265 0.06948379 0.08653631 0.09540429 0.09867279] [ 0.13640413 0.12350919 0.11931446 0.11017442 0.08921032 0.03812265 0. 0.0432744 0.06659013 0.07782774 0.08180184] [ 0.14858429 0.13684198 0.13306821 0.12493836 0.10691273 0.06948379 0.0432744 0. 0.03212291 0.0498402 0.0559074 ] [ 0.15726122 0.14621739 0.14269179 0.13514213 0.11867642 0.08653631 0.06659013 0.03212291 0. 0.02311229 0.03246395] [ 0.16231168 0.15163613 0.14823946 0.14098718 0.125292 0.09540429 0.07782774 0.0498402 0.02311229 0. 0.01183603] [ 0.1642542 0.15371362 0.15036389 0.14321922 0.12779847 0.09867279 0.08180184 0.0559074 0.03246395 0.01183603 0. ]] Replica 7 / 40 Computing statistical inefficiencies: lambda 0: g = 1.390 lambda 1: g = 1.553 lambda 2: g = 1.198 lambda 3: g = 1.895 lambda 4: g = 1.620 lambda 5: g = 1.814 lambda 6: g = 2.713 lambda 7: g = 1.558 lambda 8: g = 1.432 lambda 9: g = 1.794 lambda 10: g = 2.641 Subsampling data to produce uncorrelated samples... number of samples per lambda: [354 430 480 431 362 476 291 170 259 495 439] Method: EXP Forward EXP: Interval 1, DeltaF=7.0258 +/- 0.4661, Sum=4.1616 +/- 0.1287 Interval 2, DeltaF=1.8451 +/- 0.2945, Sum=5.2546 +/- 0.1386 Interval 3, DeltaF=3.4221 +/- 0.3594, Sum=7.2817 +/- 0.1583 Interval 4, DeltaF=4.1448 +/- 0.3770, Sum=9.7368 +/- 0.1793 Interval 5, DeltaF=1.8565 +/- 0.7106, Sum=10.8364 +/- 0.3487 Interval 6, DeltaF=-0.4335 +/- 0.3656, Sum=10.5797 +/- 0.3576 Interval 7, DeltaF=-1.3003 +/- 0.4942, Sum=9.8094 +/- 0.3858 Interval 8, DeltaF=-2.1951 +/- 0.3566, Sum=8.5092 +/- 0.3931 Interval 9, DeltaF=-2.9413 +/- 0.2922, Sum=6.7669 +/- 0.3963 Interval 10, DeltaF=-1.1098 +/- 0.1678, Sum=6.1095 +/- 0.3967 Forward EXP free energy: 6.1095 +/- 0.3967 Reverse EXP: Interval 1, DeltaF=6.8148 +/- 0.4430, Sum=4.0366 +/- 0.1163 Interval 2, DeltaF=1.9324 +/- 0.3311, Sum=5.1813 +/- 0.1332 Interval 3, DeltaF=3.1772 +/- 0.3580, Sum=7.0632 +/- 0.1533 Interval 4, DeltaF=3.3126 +/- 0.3977, Sum=9.0254 +/- 0.1796 Interval 5, DeltaF=1.1368 +/- 0.4686, Sum=9.6988 +/- 0.2218 Interval 6, DeltaF=-0.3513 +/- 0.3153, Sum=9.4907 +/- 0.2295 Interval 7, DeltaF=-1.5657 +/- 0.4007, Sum=8.5632 +/- 0.2484 Interval 8, DeltaF=-2.3370 +/- 0.3046, Sum=7.1790 +/- 0.2544 Interval 9, DeltaF=-3.0613 +/- 0.2442, Sum=5.3656 +/- 0.2569 Interval 10, DeltaF=-1.0826 +/- 0.1901, Sum=4.7244 +/- 0.2578 Reverse EXP free energy: 4.7244 +/- 0.2578 Averge of forward and reverse EXP: Interval 1, DeltaF=6.9203 +/- 0.1593, Sum=4.0991 +/- 0.0150 Interval 2, DeltaF=1.8888 +/- 0.0761, Sum=5.2179 +/- 0.0154 Interval 3, DeltaF=3.2997 +/- 0.0990, Sum=7.1724 +/- 0.0165 Interval 4, DeltaF=3.7287 +/- 0.1157, Sum=9.3811 +/- 0.0183 Interval 5, DeltaF=1.4966 +/- 0.2997, Sum=10.2676 +/- 0.0563 Interval 6, DeltaF=-0.3924 +/- 0.0907, Sum=10.0352 +/- 0.0565 Interval 7, DeltaF=-1.4330 +/- 0.1591, Sum=9.1863 +/- 0.0584 Interval 8, DeltaF=-2.2661 +/- 0.0857, Sum=7.8441 +/- 0.0586 Interval 9, DeltaF=-3.0013 +/- 0.0567, Sum=6.0663 +/- 0.0586 Interval 10, DeltaF=-1.0962 +/- 0.0249, Sum=5.4170 +/- 0.0586 Average EXP free energy: 5.4170 +/- 0.0586 Interval 1, DeltaF=6.8148 +/- 0.1511, Sum=4.0366 +/- 0.0135 Interval 2, DeltaF=1.8451 +/- 0.2457, Sum=5.1296 +/- 0.0382 Interval 3, DeltaF=3.1772 +/- 0.2638, Sum=7.0115 +/- 0.0562 Interval 4, DeltaF=4.1448 +/- 0.3108, Sum=9.4667 +/- 0.0802 Interval 5, DeltaF=1.1368 +/- 0.3709, Sum=10.1400 +/- 0.1143 Interval 6, DeltaF=-0.4335 +/- 0.6490, Sum=9.8832 +/- 0.2745 Interval 7, DeltaF=-1.5657 +/- 0.4394, Sum=8.9558 +/- 0.2973 Interval 8, DeltaF=-2.1951 +/- 0.7156, Sum=7.6556 +/- 0.4247 Interval 9, DeltaF=-3.0613 +/- 0.4697, Sum=5.8423 +/- 0.4444 Interval 10, DeltaF=-1.1098 +/- 0.7285, Sum=5.1849 +/- 0.5444 Double-Wide EXP free energy: 5.1849 +/- 0.5444 Method: BAR Interval 1, DeltaF=6.7826 +/- 0.3064, Sum=4.0176 +/- 0.0556 Interval 2, DeltaF=1.9051 +/- 0.2028, Sum=5.1460 +/- 0.0607 Interval 3, DeltaF=3.1950 +/- 0.2509, Sum=7.0385 +/- 0.0713 Interval 4, DeltaF=3.3828 +/- 0.2976, Sum=9.0423 +/- 0.0885 Interval 5, DeltaF=1.2626 +/- 0.3188, Sum=9.7902 +/- 0.1070 Interval 6, DeltaF=-0.4645 +/- 0.2351, Sum=9.5151 +/- 0.1119 Interval 7, DeltaF=-1.4907 +/- 0.2909, Sum=8.6321 +/- 0.1226 Interval 8, DeltaF=-2.2488 +/- 0.2591, Sum=7.3001 +/- 0.1289 Interval 9, DeltaF=-2.9339 +/- 0.2093, Sum=5.5622 +/- 0.1315 Interval 10, DeltaF=-1.0997 +/- 0.1389, Sum=4.9108 +/- 0.1320 BAR free energy: 4.9108 +/- 0.1320 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9738 +/- 0.4534, Sum=4.1309 +/- 0.1218 Interval 2, DeltaF=1.8906 +/- 0.2491, Sum=5.2507 +/- 0.1272 Interval 3, DeltaF=3.2567 +/- 0.3316, Sum=7.1798 +/- 0.1429 Interval 4, DeltaF=3.5605 +/- 0.3951, Sum=9.2888 +/- 0.1702 Interval 5, DeltaF=1.3424 +/- 0.3500, Sum=10.0839 +/- 0.1850 Interval 6, DeltaF=-0.4586 +/- 0.2196, Sum=9.8123 +/- 0.1872 Interval 7, DeltaF=-1.5269 +/- 0.2570, Sum=8.9078 +/- 0.1913 Interval 8, DeltaF=-2.2842 +/- 0.3723, Sum=7.5548 +/- 0.2082 Interval 9, DeltaF=-3.0212 +/- 0.4063, Sum=5.7652 +/- 0.2300 Interval 10, DeltaF=-1.0949 +/- 0.1904, Sum=5.1167 +/- 0.2310 Unopt. BAR free energy: 5.1167 +/- 0.2310 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7842 +/- 0.3080, Sum=4.0185 +/- 0.0562 Interval 2, DeltaF=1.9053 +/- 0.2040, Sum=5.1471 +/- 0.0614 Interval 3, DeltaF=3.1957 +/- 0.2532, Sum=7.0401 +/- 0.0722 Interval 4, DeltaF=3.3940 +/- 0.3092, Sum=9.0505 +/- 0.0917 Interval 5, DeltaF=1.2791 +/- 0.3253, Sum=9.8081 +/- 0.1111 Interval 6, DeltaF=-0.4586 +/- 0.2196, Sum=9.5365 +/- 0.1147 Interval 7, DeltaF=-1.5051 +/- 0.2738, Sum=8.6449 +/- 0.1230 Interval 8, DeltaF=-2.2504 +/- 0.2657, Sum=7.3119 +/- 0.1299 Interval 9, DeltaF=-2.9326 +/- 0.2060, Sum=5.5749 +/- 0.1323 Interval 10, DeltaF=-1.0993 +/- 0.1378, Sum=4.9237 +/- 0.1328 Postopt. BAR free energy: 4.9237 +/- 0.1328 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 784 N_k = [354 430] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.43010735] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.79565823] relative max_delta = 2.847473e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9931 relative max_delta = 3.955238e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7636 relative max_delta = 2.617632e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7826 relative max_delta = 2.791810e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7826 relative max_delta = 1.433681e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7826 relative max_delta = 3.813273e-13 Converged to tolerance of 3.813273e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7826 Final dimensionless free energies f_k = [ 0. 6.78255993] Computing normalized weights... Interval 1, DeltaF=6.7826 +/- 0.3064, Sum=4.0176 +/- 0.0556 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 910 N_k = [430 480] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.43957188] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.77827915] relative max_delta = 1.904691e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7909 relative max_delta = 7.060996e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9048 relative max_delta = 5.977826e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9051 relative max_delta = 1.537124e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9051 relative max_delta = 1.384979e-09 Converged to tolerance of 1.384979e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9051 Final dimensionless free energies f_k = [ 0. 1.90508273] Computing normalized weights... Interval 2, DeltaF=1.9051 +/- 0.2028, Sum=5.1460 +/- 0.0607 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 911 N_k = [480 431] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.63346421] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.43293024] relative max_delta = 3.286021e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5130 relative max_delta = 3.187482e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2248 relative max_delta = 2.207213e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1950 relative max_delta = 9.334530e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1950 relative max_delta = 1.042582e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1950 relative max_delta = 1.337732e-11 Converged to tolerance of 1.337732e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1950 Final dimensionless free energies f_k = [ 0. 3.19496197] Computing normalized weights... Interval 3, DeltaF=3.1950 +/- 0.2509, Sum=7.0385 +/- 0.0713 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 793 N_k = [431 362] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.01397561] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.77246318] relative max_delta = 4.279285e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9711 relative max_delta = 1.007553e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6676 relative max_delta = 4.625715e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3920 relative max_delta = 8.123069e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3828 relative max_delta = 2.729786e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3828 relative max_delta = 3.059662e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3828 relative max_delta = 3.840173e-12 Converged to tolerance of 3.840173e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3828 Final dimensionless free energies f_k = [ 0. 3.38278983] Computing normalized weights... Interval 4, DeltaF=3.3828 +/- 0.2976, Sum=9.0423 +/- 0.0885 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 838 N_k = [362 476] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.34944733] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.61181577] relative max_delta = 4.288357e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6817 relative max_delta = 1.025061e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3006 relative max_delta = 4.758666e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2628 relative max_delta = 2.995689e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2626 relative max_delta = 1.177331e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2626 relative max_delta = 1.816767e-09 Converged to tolerance of 1.816767e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2626 Final dimensionless free energies f_k = [ 0. 1.26263306] Computing normalized weights... Interval 5, DeltaF=1.2626 +/- 0.3188, Sum=9.7902 +/- 0.1070 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 767 N_k = [476 291] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.30481804] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.40830038] relative max_delta = 2.534466e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4139 relative max_delta = 1.348313e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4642 relative max_delta = 1.083423e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4645 relative max_delta = 6.159310e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4645 relative max_delta = 2.023553e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4645 relative max_delta = 9.441971e-15 Converged to tolerance of 9.441971e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4645 Final dimensionless free energies f_k = [ 0. -0.4644561] Computing normalized weights... Interval 6, DeltaF=-0.4645 +/- 0.2351, Sum=9.5151 +/- 0.1119 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 461 N_k = [291 170] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.90463411] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.24447691] relative max_delta = 2.730808e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.2685 relative max_delta = 1.891772e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.4855 relative max_delta = 1.461227e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.4907 relative max_delta = 3.432488e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.4907 relative max_delta = 1.986302e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.4907 relative max_delta = 6.637512e-13 Converged to tolerance of 6.637512e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.4907 Final dimensionless free energies f_k = [ 0. -1.49066516] Computing normalized weights... Interval 7, DeltaF=-1.4907 +/- 0.2909, Sum=8.6321 +/- 0.1226 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 429 N_k = [170 259] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.65914508] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.06731523] relative max_delta = 1.974397e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0857 relative max_delta = 8.803625e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2505 relative max_delta = 7.323095e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2488 relative max_delta = 7.699455e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2488 relative max_delta = 7.363134e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2488 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2488 Final dimensionless free energies f_k = [ 0. -2.24875006] Computing normalized weights... Interval 8, DeltaF=-2.2488 +/- 0.2591, Sum=7.3001 +/- 0.1289 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 754 N_k = [259 495] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.33245959] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.78685516] relative max_delta = 1.630496e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8018 relative max_delta = 5.349203e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9362 relative max_delta = 4.574706e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9339 relative max_delta = 7.691725e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9339 relative max_delta = 2.060306e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9339 relative max_delta = 1.574191e-14 Converged to tolerance of 1.574191e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9339 Final dimensionless free energies f_k = [ 0. -2.93390637] Computing normalized weights... Interval 9, DeltaF=-2.9339 +/- 0.2093, Sum=5.5622 +/- 0.1315 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 934 N_k = [495 439] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01196961] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.09263409] relative max_delta = 7.382570e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0933 relative max_delta = 6.422468e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0997 relative max_delta = 5.747183e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0997 relative max_delta = 7.892506e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0997 relative max_delta = 1.332683e-14 Converged to tolerance of 1.332683e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0997 Final dimensionless free energies f_k = [ 0. -1.09965708] Computing normalized weights... Interval 10, DeltaF=-1.0997 +/- 0.1389, Sum=4.9108 +/- 0.1320 Pairwise MBAR free energy: 4.9108 +/- 0.1320 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4187 N_k = [354 430 480 431 362 476 291 170 259 495 439] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.01165719 2.04885143 2.01713246 1.65315651 1.75060802 1.78849018 1.86468708 1.88660302 1.21166566 0.64021095] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.01366379 3.43001849 3.61422684 3.06355588 3.20331769 3.24532758 3.27242288 3.12778807 1.958417 1.2077714 ] relative max_delta = 4.418910e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2722 3.8147 4.4383 4.5436 4.8197 4.8197 4.7471 4.4360 3.0511 2.2618 relative max_delta = 3.353703e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7551 7.4644 11.5774 16.9159 18.3784 17.9871 16.9508 15.0244 11.7446 10.6188 relative max_delta = 7.377519e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7397 8.7488 11.9611 15.9436 17.2467 16.7802 15.2867 13.0532 10.1061 9.0106 relative max_delta = 1.142948e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7797 8.6989 11.8848 15.3326 16.6323 16.1563 14.6397 12.3741 9.4573 8.3617 relative max_delta = 4.083197e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7788 8.6992 11.8760 15.2764 16.5778 16.1018 14.5851 12.3192 9.4027 8.3071 relative max_delta = 3.390908e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7788 8.6991 11.8760 15.2760 16.5774 16.1014 14.5847 12.3188 9.4023 8.3067 relative max_delta = 2.517281e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7788 8.6991 11.8760 15.2760 16.5774 16.1014 14.5847 12.3188 9.4023 8.3067 relative max_delta = 1.395292e-09 Converged to tolerance of 1.395292e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7788 8.6991 11.8760 15.2760 16.5774 16.1014 14.5847 12.3188 9.4023 8.3067 Final dimensionless free energies f_k = [ 0. 6.77879759 8.69914848 11.87598515 15.27597109 16.57744911 16.10141438 14.58468339 12.31883635 9.40228024 8.30673586] Computing normalized weights... DeltaMij: [[ 0. 4.01533497 5.15283051 7.03458951 9.04852816 9.81944219 9.53746904 8.63905263 7.29690682 5.56932172 4.92038987] [-4.01533497 0. 1.13749555 3.01925454 5.03319319 5.80410722 5.52213408 4.62371767 3.28157185 1.55398675 0.9050549 ] [-5.15283051 -1.13749555 0. 1.881759 3.89569764 4.66661168 4.38463853 3.48622212 2.1440763 0.4164912 -0.23244064] [-7.03458951 -3.01925454 -1.881759 0. 2.01393865 2.78485268 2.50287953 1.60446312 0.26231731 -1.46526779 -2.11419964] [-9.04852816 -5.03319319 -3.89569764 -2.01393865 0. 0.77091403 0.48894089 -0.40947552 -1.75162134 -3.47920644 -4.12813829] [-9.81944219 -5.80410722 -4.66661168 -2.78485268 -0.77091403 0. -0.28197315 -1.18038956 -2.52253537 -4.25012047 -4.89905232] [-9.53746904 -5.52213408 -4.38463853 -2.50287953 -0.48894089 0.28197315 0. -0.89841641 -2.24056223 -3.96814733 -4.61707918] [-8.63905263 -4.62371767 -3.48622212 -1.60446312 0.40947552 1.18038956 0.89841641 0. -1.34214582 -3.06973092 -3.71866277] [-7.29690682 -3.28157185 -2.1440763 -0.26231731 1.75162134 2.52253537 2.24056223 1.34214582 0. -1.7275851 -2.37651695] [-5.56932172 -1.55398675 -0.4164912 1.46526779 3.47920644 4.25012047 3.96814733 3.06973092 1.7275851 0. -0.64893185] [-4.92038987 -0.9050549 0.23244064 2.11419964 4.12813829 4.89905232 4.61707918 3.71866277 2.37651695 0.64893185 0. ]] dDeltaMij: [[ 0. 0.0546833 0.0677583 0.08009066 0.09918525 0.12124551 0.12945187 0.1423709 0.15415526 0.15981554 0.16151497] [ 0.0546833 0. 0.02308288 0.04766639 0.07549078 0.10277005 0.1123343 0.12700662 0.14008945 0.14629496 0.14814957] [ 0.0677583 0.02308288 0. 0.0343534 0.06815741 0.09751079 0.10754378 0.12278986 0.13627811 0.14264952 0.14455091] [ 0.08009066 0.04766639 0.0343534 0. 0.05157827 0.08666959 0.09782164 0.11437108 0.12874439 0.13547058 0.1374713 ] [ 0.09918525 0.07549078 0.06815741 0.05157827 0. 0.05795648 0.07354642 0.09445382 0.11142638 0.11913439 0.12140462] [ 0.12124551 0.10277005 0.09751079 0.08666959 0.05795648 0. 0.03194144 0.06690016 0.08930313 0.0987517 0.10147886] [ 0.12945187 0.1123343 0.10754378 0.09782164 0.07354642 0.03194144 0. 0.04579676 0.07402836 0.08524205 0.0883882 ] [ 0.1423709 0.12700662 0.12278986 0.11437108 0.09445382 0.06690016 0.04579676 0. 0.03695965 0.05397223 0.05886516] [ 0.15415526 0.14008945 0.13627811 0.12874439 0.11142638 0.08930313 0.07402836 0.03695965 0. 0.02251236 0.03073589] [ 0.15981554 0.14629496 0.14264952 0.13547058 0.11913439 0.0987517 0.08524205 0.05397223 0.02251236 0. 0.01076306] [ 0.16151497 0.14814957 0.14455091 0.1374713 0.12140462 0.10147886 0.0883882 0.05886516 0.03073589 0.01076306 0. ]] Replica 8 / 40 Computing statistical inefficiencies: lambda 0: g = 1.569 lambda 1: g = 1.881 lambda 2: g = 1.613 lambda 3: g = 1.222 lambda 4: g = 1.771 lambda 5: g = 1.127 lambda 6: g = 1.541 lambda 7: g = 1.459 lambda 8: g = 2.122 lambda 9: g = 1.853 lambda 10: g = 1.776 Subsampling data to produce uncorrelated samples... number of samples per lambda: [373 323 500 391 500 500 337 166 155 500 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.6597 +/- 0.4951, Sum=3.9448 +/- 0.1452 Interval 2, DeltaF=1.9277 +/- 0.2737, Sum=5.0866 +/- 0.1518 Interval 3, DeltaF=3.5424 +/- 0.3378, Sum=7.1849 +/- 0.1662 Interval 4, DeltaF=4.1514 +/- 0.3771, Sum=9.6439 +/- 0.1863 Interval 5, DeltaF=2.0127 +/- 0.5690, Sum=10.8361 +/- 0.2674 Interval 6, DeltaF=-0.3855 +/- 0.2886, Sum=10.6077 +/- 0.2719 Interval 7, DeltaF=-1.5540 +/- 0.3939, Sum=9.6872 +/- 0.2870 Interval 8, DeltaF=-2.3717 +/- 0.3642, Sum=8.2824 +/- 0.2976 Interval 9, DeltaF=-2.8260 +/- 0.3741, Sum=6.6084 +/- 0.3089 Interval 10, DeltaF=-1.0481 +/- 0.1618, Sum=5.9876 +/- 0.3093 Forward EXP free energy: 5.9876 +/- 0.3093 Reverse EXP: Interval 1, DeltaF=6.3796 +/- 0.4228, Sum=3.7789 +/- 0.1059 Interval 2, DeltaF=1.9037 +/- 0.3109, Sum=4.9065 +/- 0.1204 Interval 3, DeltaF=3.1868 +/- 0.3609, Sum=6.7941 +/- 0.1430 Interval 4, DeltaF=3.5340 +/- 0.3822, Sum=8.8874 +/- 0.1671 Interval 5, DeltaF=1.3964 +/- 0.4294, Sum=9.7146 +/- 0.1996 Interval 6, DeltaF=-0.4666 +/- 0.2959, Sum=9.4382 +/- 0.2063 Interval 7, DeltaF=-1.5719 +/- 0.4114, Sum=8.5071 +/- 0.2293 Interval 8, DeltaF=-1.9628 +/- 0.3941, Sum=7.3445 +/- 0.2471 Interval 9, DeltaF=-2.9999 +/- 0.2355, Sum=5.5675 +/- 0.2493 Interval 10, DeltaF=-1.0331 +/- 0.1846, Sum=4.9556 +/- 0.2501 Reverse EXP free energy: 4.9556 +/- 0.2501 Averge of forward and reverse EXP: Interval 1, DeltaF=6.5196 +/- 0.1651, Sum=3.8618 +/- 0.0161 Interval 2, DeltaF=1.9157 +/- 0.0666, Sum=4.9965 +/- 0.0164 Interval 3, DeltaF=3.3646 +/- 0.0942, Sum=6.9895 +/- 0.0172 Interval 4, DeltaF=3.8427 +/- 0.1109, Sum=9.2657 +/- 0.0187 Interval 5, DeltaF=1.7046 +/- 0.2028, Sum=10.2753 +/- 0.0307 Interval 6, DeltaF=-0.4260 +/- 0.0658, Sum=10.0230 +/- 0.0308 Interval 7, DeltaF=-1.5630 +/- 0.1250, Sum=9.0972 +/- 0.0322 Interval 8, DeltaF=-2.1673 +/- 0.1111, Sum=7.8134 +/- 0.0330 Interval 9, DeltaF=-2.9129 +/- 0.0819, Sum=6.0880 +/- 0.0332 Interval 10, DeltaF=-1.0406 +/- 0.0234, Sum=5.4716 +/- 0.0332 Average EXP free energy: 5.4716 +/- 0.0332 Interval 1, DeltaF=6.3796 +/- 0.1376, Sum=3.7789 +/- 0.0112 Interval 2, DeltaF=1.9277 +/- 0.2729, Sum=4.9207 +/- 0.0455 Interval 3, DeltaF=3.1868 +/- 0.2428, Sum=6.8083 +/- 0.0574 Interval 4, DeltaF=4.1514 +/- 0.3244, Sum=9.2673 +/- 0.0847 Interval 5, DeltaF=1.3964 +/- 0.3383, Sum=10.0945 +/- 0.1085 Interval 6, DeltaF=-0.3855 +/- 0.4955, Sum=9.8661 +/- 0.1814 Interval 7, DeltaF=-1.5719 +/- 0.4008, Sum=8.9350 +/- 0.2049 Interval 8, DeltaF=-2.3717 +/- 0.5372, Sum=7.5302 +/- 0.2668 Interval 9, DeltaF=-2.9999 +/- 0.4561, Sum=5.7533 +/- 0.2939 Interval 10, DeltaF=-1.0481 +/- 0.5680, Sum=5.1324 +/- 0.3505 Double-Wide EXP free energy: 5.1324 +/- 0.3505 Method: BAR Interval 1, DeltaF=6.6834 +/- 0.3207, Sum=3.9588 +/- 0.0609 Interval 2, DeltaF=1.9081 +/- 0.2037, Sum=5.0891 +/- 0.0657 Interval 3, DeltaF=3.2864 +/- 0.2481, Sum=7.0357 +/- 0.0751 Interval 4, DeltaF=3.4797 +/- 0.2844, Sum=9.0969 +/- 0.0891 Interval 5, DeltaF=1.2962 +/- 0.3083, Sum=9.8647 +/- 0.1054 Interval 6, DeltaF=-0.5520 +/- 0.2343, Sum=9.5377 +/- 0.1103 Interval 7, DeltaF=-1.6476 +/- 0.2916, Sum=8.5617 +/- 0.1212 Interval 8, DeltaF=-2.1988 +/- 0.2768, Sum=7.2593 +/- 0.1295 Interval 9, DeltaF=-2.8339 +/- 0.2238, Sum=5.5807 +/- 0.1328 Interval 10, DeltaF=-1.0519 +/- 0.1369, Sum=4.9576 +/- 0.1333 BAR free energy: 4.9576 +/- 0.1333 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.6334 +/- 0.5161, Sum=3.9292 +/- 0.1578 Interval 2, DeltaF=1.9214 +/- 0.2275, Sum=5.0673 +/- 0.1607 Interval 3, DeltaF=3.3918 +/- 0.3504, Sum=7.0764 +/- 0.1764 Interval 4, DeltaF=3.5418 +/- 0.3649, Sum=9.1743 +/- 0.1933 Interval 5, DeltaF=1.3221 +/- 0.3435, Sum=9.9574 +/- 0.2055 Interval 6, DeltaF=-0.5360 +/- 0.2199, Sum=9.6399 +/- 0.2075 Interval 7, DeltaF=-1.6292 +/- 0.2455, Sum=8.6749 +/- 0.2105 Interval 8, DeltaF=-2.0639 +/- 0.3474, Sum=7.4524 +/- 0.2223 Interval 9, DeltaF=-2.9532 +/- 0.4755, Sum=5.7031 +/- 0.2596 Interval 10, DeltaF=-1.0485 +/- 0.1937, Sum=5.0820 +/- 0.2605 Unopt. BAR free energy: 5.0820 +/- 0.2605 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6933 +/- 0.3207, Sum=3.9647 +/- 0.0609 Interval 2, DeltaF=1.9069 +/- 0.2069, Sum=5.0942 +/- 0.0660 Interval 3, DeltaF=3.2931 +/- 0.2526, Sum=7.0449 +/- 0.0761 Interval 4, DeltaF=3.4803 +/- 0.2939, Sum=9.1064 +/- 0.0917 Interval 5, DeltaF=1.3014 +/- 0.3165, Sum=9.8773 +/- 0.1092 Interval 6, DeltaF=-0.5620 +/- 0.2496, Sum=9.5444 +/- 0.1153 Interval 7, DeltaF=-1.6505 +/- 0.3062, Sum=8.5667 +/- 0.1280 Interval 8, DeltaF=-2.1870 +/- 0.2766, Sum=7.2713 +/- 0.1357 Interval 9, DeltaF=-2.8273 +/- 0.2070, Sum=5.5966 +/- 0.1381 Interval 10, DeltaF=-1.0518 +/- 0.1373, Sum=4.9736 +/- 0.1386 Postopt. BAR free energy: 4.9736 +/- 0.1386 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 696 N_k = [373 323] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.57048357] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.84656234] relative max_delta = 2.632956e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0311 relative max_delta = 3.667246e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6836 relative max_delta = 2.472544e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6834 relative max_delta = 3.198363e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6834 relative max_delta = 1.058135e-11 Converged to tolerance of 1.058135e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6834 Final dimensionless free energies f_k = [ 0. 6.68340437] Computing normalized weights... Interval 1, DeltaF=6.6834 +/- 0.3207, Sum=3.9588 +/- 0.0609 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 823 N_k = [323 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.4685439] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.79818117] relative max_delta = 1.833171e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8091 relative max_delta = 6.024926e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9073 relative max_delta = 5.151696e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9081 relative max_delta = 3.946613e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9081 relative max_delta = 2.521727e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.9081 relative max_delta = 3.491095e-16 Converged to tolerance of 3.491095e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9081 Final dimensionless free energies f_k = [ 0. 1.90809427] Computing normalized weights... Interval 2, DeltaF=1.9081 +/- 0.2037, Sum=5.0891 +/- 0.0657 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 891 N_k = [500 391] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.77486204] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.58766529] relative max_delta = 3.141068e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6614 relative max_delta = 2.770264e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3160 relative max_delta = 1.974167e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2864 relative max_delta = 9.017410e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2864 relative max_delta = 1.332948e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2864 relative max_delta = 2.971982e-11 Converged to tolerance of 2.971982e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2864 Final dimensionless free energies f_k = [ 0. 3.28635462] Computing normalized weights... Interval 3, DeltaF=3.2864 +/- 0.2481, Sum=7.0357 +/- 0.0751 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 891 N_k = [391 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.07711429] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.87912157] relative max_delta = 4.267990e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0664 relative max_delta = 9.063317e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6858 relative max_delta = 4.393628e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4828 relative max_delta = 5.829252e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4797 relative max_delta = 8.852123e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4797 relative max_delta = 2.116030e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4797 relative max_delta = 1.110314e-14 Converged to tolerance of 1.110314e-14 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4797 Final dimensionless free energies f_k = [ 0. 3.4797156] Computing normalized weights... Interval 4, DeltaF=3.4797 +/- 0.2844, Sum=9.0969 +/- 0.0891 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.34316739] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.60477529] relative max_delta = 4.325704e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6803 relative max_delta = 1.110292e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3467 relative max_delta = 4.948262e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2965 relative max_delta = 3.868927e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2962 relative max_delta = 2.425295e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2962 relative max_delta = 9.482758e-09 Converged to tolerance of 9.482758e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2962 Final dimensionless free energies f_k = [ 0. 1.29620817] Computing normalized weights... Interval 5, DeltaF=1.2962 +/- 0.3083, Sum=9.8647 +/- 0.1054 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 837 N_k = [500 337] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.35206447] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.47759588] relative max_delta = 2.628402e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4850 relative max_delta = 1.524073e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5516 relative max_delta = 1.207802e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5520 relative max_delta = 7.934088e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5520 relative max_delta = 3.508912e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5520 relative max_delta = 8.044377e-16 Converged to tolerance of 8.044377e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5520 Final dimensionless free energies f_k = [ 0. -0.55204919] Computing normalized weights... Interval 6, DeltaF=-0.5520 +/- 0.2343, Sum=9.5377 +/- 0.1103 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 503 N_k = [337 166] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97614628] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35694889] relative max_delta = 2.806315e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3851 relative max_delta = 2.029473e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6397 relative max_delta = 1.553077e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6475 relative max_delta = 4.748755e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6476 relative max_delta = 4.586479e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6476 relative max_delta = 4.281589e-12 Converged to tolerance of 4.281589e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6476 Final dimensionless free energies f_k = [ 0. -1.64755064] Computing normalized weights... Interval 7, DeltaF=-1.6476 +/- 0.2916, Sum=8.5617 +/- 0.1212 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 321 N_k = [166 155] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.56381333] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.99711113] relative max_delta = 2.169623e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0173 relative max_delta = 9.999518e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.1988 relative max_delta = 8.254632e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.1988 relative max_delta = 2.005158e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.1988 relative max_delta = 8.401982e-14 Converged to tolerance of 8.401982e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.1988 Final dimensionless free energies f_k = [ 0. -2.19878015] Computing normalized weights... Interval 8, DeltaF=-2.1988 +/- 0.2768, Sum=7.2593 +/- 0.1295 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 655 N_k = [155 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.2921925] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.71169318] relative max_delta = 1.547006e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7242 relative max_delta = 4.599263e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8364 relative max_delta = 3.953780e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8339 relative max_delta = 8.812134e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8339 relative max_delta = 4.350976e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8339 relative max_delta = 1.075016e-13 Converged to tolerance of 1.075016e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8339 Final dimensionless free energies f_k = [ 0. -2.83386779] Computing normalized weights... Interval 9, DeltaF=-2.8339 +/- 0.2238, Sum=5.5807 +/- 0.1328 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96875462] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.04516568] relative max_delta = 7.310904e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0458 relative max_delta = 6.432933e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0519 relative max_delta = 5.756277e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0519 relative max_delta = 1.366414e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0519 relative max_delta = 3.377447e-15 Converged to tolerance of 3.377447e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0519 Final dimensionless free energies f_k = [ 0. -1.05189331] Computing normalized weights... Interval 10, DeltaF=-1.0519 +/- 0.1369, Sum=4.9576 +/- 0.1333 Pairwise MBAR free energy: 4.9576 +/- 0.1333 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4245 N_k = [373 323 500 391 500 500 337 166 155 500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.94102305 2.0094576 1.79266382 1.60540495 1.70439182 1.67674559 1.6871093 1.71640126 1.19295871 0.67178021] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.85036538 3.28829035 3.2430816 2.95837121 3.09423748 3.04256733 2.98098121 2.86794277 1.93234507 1.24900314] relative max_delta = 4.410857e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0870 3.6440 4.1269 4.4612 4.7347 4.6397 4.4785 4.2177 3.0633 2.3380 relative max_delta = 3.464762e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.3685 7.0291 11.6450 16.8597 18.3275 17.8352 16.7136 14.9817 11.8286 10.7364 relative max_delta = 7.416610e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6362 8.6913 11.9248 15.9468 17.2489 16.7123 15.1386 12.9314 10.0306 8.9868 relative max_delta = 1.188617e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6771 8.5707 11.8754 15.4020 16.6995 16.1549 14.5540 12.2958 9.4393 8.3939 relative max_delta = 3.806313e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6745 8.5713 11.8646 15.3670 16.6654 16.1208 14.5198 12.2608 9.4050 8.3597 relative max_delta = 2.101496e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6745 8.5713 11.8646 15.3669 16.6653 16.1207 14.5197 12.2607 9.4049 8.3595 relative max_delta = 7.539657e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6745 8.5713 11.8646 15.3669 16.6653 16.1207 14.5197 12.2607 9.4049 8.3595 relative max_delta = 9.822731e-11 Converged to tolerance of 9.822731e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6745 8.5713 11.8646 15.3669 16.6653 16.1207 14.5197 12.2607 9.4049 8.3595 Final dimensionless free energies f_k = [ 0. 6.67449705 8.57132092 11.86458805 15.36685759 16.66528114 16.12067842 14.51967527 12.26069423 9.40490475 8.35953162] Computing normalized weights... DeltaMij: [[ 0. 3.95355386 5.07711348 7.02783858 9.10236362 9.87146839 9.54887985 8.6005459 7.26246707 5.57087631 4.95166276] [-3.95355386 0. 1.12355962 3.07428472 5.14880976 5.91791452 5.59532599 4.64699204 3.3089132 1.61732245 0.9981089 ] [-5.07711348 -1.12355962 0. 1.9507251 4.02525015 4.79435491 4.47176637 3.52343242 2.18535359 0.49376283 -0.12545071] [-7.02783858 -3.07428472 -1.9507251 0. 2.07452504 2.8436298 2.52104127 1.57270732 0.23462848 -1.45696227 -2.07617582] [-9.10236362 -5.14880976 -4.02525015 -2.07452504 0. 0.76910476 0.44651623 -0.50181773 -1.83989656 -3.53148731 -4.15070086] [-9.87146839 -5.91791452 -4.79435491 -2.8436298 -0.76910476 0. -0.32258853 -1.27092249 -2.60900132 -4.30059208 -4.91980562] [-9.54887985 -5.59532599 -4.47176637 -2.52104127 -0.44651623 0.32258853 0. -0.94833395 -2.28641279 -3.97800354 -4.59721709] [-8.6005459 -4.64699204 -3.52343242 -1.57270732 0.50181773 1.27092249 0.94833395 0. -1.33807883 -3.02966959 -3.64888313] [-7.26246707 -3.3089132 -2.18535359 -0.23462848 1.83989656 2.60900132 2.28641279 1.33807883 0. -1.69159076 -2.3108043 ] [-5.57087631 -1.61732245 -0.49376283 1.45696227 3.53148731 4.30059208 3.97800354 3.02966959 1.69159076 0. -0.61921355] [-4.95166276 -0.9981089 0.12545071 2.07617582 4.15070086 4.91980562 4.59721709 3.64888313 2.3108043 0.61921355 0. ]] dDeltaMij: [[ 0. 0.05946139 0.07306905 0.08443814 0.10002167 0.11872021 0.1267318 0.13941363 0.15241895 0.15933248 0.16117525] [ 0.05946139 0. 0.02306511 0.04703737 0.07135026 0.09581803 0.10558198 0.12051043 0.13534452 0.14308544 0.14513465] [ 0.07306905 0.02306511 0. 0.03369472 0.06362498 0.09021345 0.10052326 0.11610399 0.13143634 0.13939446 0.14149713] [ 0.08443814 0.04703737 0.03369472 0. 0.04632606 0.07890784 0.09051553 0.10755584 0.12395013 0.13235912 0.13457177] [ 0.10002167 0.07135026 0.06362498 0.04632606 0. 0.05430574 0.07007354 0.09102747 0.1099151 0.11931737 0.12176724] [ 0.11872021 0.09581803 0.09021345 0.07890784 0.05430574 0. 0.03148099 0.06571679 0.09010598 0.10136072 0.10423332] [ 0.1267318 0.10558198 0.10052326 0.09051553 0.07007354 0.03148099 0. 0.04559731 0.07600133 0.08911526 0.09237226] [ 0.13941363 0.12051043 0.11610399 0.10755584 0.09102747 0.06571679 0.04559731 0. 0.03938914 0.05828309 0.06314387] [ 0.15241895 0.13534452 0.13143634 0.12395013 0.1099151 0.09010598 0.07600133 0.03938914 0. 0.02383186 0.03188462] [ 0.15933248 0.14308544 0.13939446 0.13235912 0.11931737 0.10136072 0.08911526 0.05828309 0.02383186 0. 0.01071181] [ 0.16117525 0.14513465 0.14149713 0.13457177 0.12176724 0.10423332 0.09237226 0.06314387 0.03188462 0.01071181 0. ]] Replica 9 / 40 Computing statistical inefficiencies: lambda 0: g = 2.615 lambda 1: g = 2.124 lambda 2: g = 1.616 lambda 3: g = 1.639 lambda 4: g = 1.845 lambda 5: g = 1.322 lambda 6: g = 2.155 lambda 7: g = 1.725 lambda 8: g = 1.000 lambda 9: g = 1.852 lambda 10: g = 1.621 Subsampling data to produce uncorrelated samples... number of samples per lambda: [354 500 500 500 500 367 179 211 194 500 485] Method: EXP Forward EXP: Interval 1, DeltaF=6.6091 +/- 0.4755, Sum=3.9148 +/- 0.1339 Interval 2, DeltaF=1.9683 +/- 0.2377, Sum=5.0808 +/- 0.1381 Interval 3, DeltaF=3.5716 +/- 0.3158, Sum=7.1964 +/- 0.1502 Interval 4, DeltaF=3.4635 +/- 0.6150, Sum=9.2479 +/- 0.2697 Interval 5, DeltaF=1.7420 +/- 0.4661, Sum=10.2797 +/- 0.2988 Interval 6, DeltaF=-0.6689 +/- 0.3300, Sum=9.8835 +/- 0.3057 Interval 7, DeltaF=-1.7289 +/- 0.5120, Sum=8.8594 +/- 0.3429 Interval 8, DeltaF=-2.0385 +/- 0.3076, Sum=7.6519 +/- 0.3474 Interval 9, DeltaF=-3.0106 +/- 0.3097, Sum=5.8686 +/- 0.3520 Interval 10, DeltaF=-1.0809 +/- 0.1615, Sum=5.2284 +/- 0.3524 Forward EXP free energy: 5.2284 +/- 0.3524 Reverse EXP: Interval 1, DeltaF=6.5177 +/- 0.4849, Sum=3.8607 +/- 0.1393 Interval 2, DeltaF=1.9211 +/- 0.3007, Sum=4.9987 +/- 0.1492 Interval 3, DeltaF=3.1618 +/- 0.3771, Sum=6.8715 +/- 0.1714 Interval 4, DeltaF=3.4717 +/- 0.3635, Sum=8.9279 +/- 0.1884 Interval 5, DeltaF=1.1524 +/- 0.4962, Sum=9.6106 +/- 0.2383 Interval 6, DeltaF=-0.5881 +/- 0.3703, Sum=9.2622 +/- 0.2517 Interval 7, DeltaF=-1.4977 +/- 0.3535, Sum=8.3751 +/- 0.2624 Interval 8, DeltaF=-2.5347 +/- 0.3387, Sum=6.8737 +/- 0.2710 Interval 9, DeltaF=-3.0115 +/- 0.2488, Sum=5.0899 +/- 0.2735 Interval 10, DeltaF=-1.0635 +/- 0.1871, Sum=4.4600 +/- 0.2743 Reverse EXP free energy: 4.4600 +/- 0.2743 Averge of forward and reverse EXP: Interval 1, DeltaF=6.5634 +/- 0.1775, Sum=3.8878 +/- 0.0187 Interval 2, DeltaF=1.9447 +/- 0.0580, Sum=5.0397 +/- 0.0188 Interval 3, DeltaF=3.3667 +/- 0.0945, Sum=7.0339 +/- 0.0195 Interval 4, DeltaF=3.4676 +/- 0.2180, Sum=9.0879 +/- 0.0343 Interval 5, DeltaF=1.4472 +/- 0.1787, Sum=9.9452 +/- 0.0391 Interval 6, DeltaF=-0.6285 +/- 0.0953, Sum=9.5729 +/- 0.0395 Interval 7, DeltaF=-1.6133 +/- 0.1580, Sum=8.6173 +/- 0.0422 Interval 8, DeltaF=-2.2866 +/- 0.0809, Sum=7.2628 +/- 0.0424 Interval 9, DeltaF=-3.0110 +/- 0.0621, Sum=5.4793 +/- 0.0424 Interval 10, DeltaF=-1.0722 +/- 0.0238, Sum=4.8442 +/- 0.0424 Average EXP free energy: 4.8442 +/- 0.0424 Interval 1, DeltaF=6.5177 +/- 0.1810, Sum=3.8607 +/- 0.0194 Interval 2, DeltaF=1.9683 +/- 0.2499, Sum=5.0266 +/- 0.0418 Interval 3, DeltaF=3.1618 +/- 0.2952, Sum=6.8995 +/- 0.0664 Interval 4, DeltaF=3.4635 +/- 0.4011, Sum=8.9510 +/- 0.1162 Interval 5, DeltaF=1.1524 +/- 0.3947, Sum=9.6337 +/- 0.1483 Interval 6, DeltaF=-0.6689 +/- 0.5555, Sum=9.2374 +/- 0.2354 Interval 7, DeltaF=-1.4977 +/- 0.4724, Sum=8.3503 +/- 0.2700 Interval 8, DeltaF=-2.0385 +/- 0.6343, Sum=7.1428 +/- 0.3601 Interval 9, DeltaF=-3.0115 +/- 0.5003, Sum=5.3590 +/- 0.3894 Interval 10, DeltaF=-1.0809 +/- 0.6472, Sum=4.7187 +/- 0.4617 Double-Wide EXP free energy: 4.7187 +/- 0.4617 Method: BAR Interval 1, DeltaF=6.5991 +/- 0.3033, Sum=3.9089 +/- 0.0545 Interval 2, DeltaF=1.9260 +/- 0.1906, Sum=5.0497 +/- 0.0586 Interval 3, DeltaF=3.1787 +/- 0.2450, Sum=6.9326 +/- 0.0685 Interval 4, DeltaF=3.3908 +/- 0.2799, Sum=8.9411 +/- 0.0828 Interval 5, DeltaF=1.0333 +/- 0.3346, Sum=9.5531 +/- 0.1061 Interval 6, DeltaF=-0.7850 +/- 0.2710, Sum=9.0882 +/- 0.1146 Interval 7, DeltaF=-1.6031 +/- 0.2919, Sum=8.1386 +/- 0.1253 Interval 8, DeltaF=-2.2972 +/- 0.2668, Sum=6.7779 +/- 0.1322 Interval 9, DeltaF=-2.9749 +/- 0.2109, Sum=5.0157 +/- 0.1348 Interval 10, DeltaF=-1.0859 +/- 0.1372, Sum=4.3725 +/- 0.1352 BAR free energy: 4.3725 +/- 0.1352 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.5728 +/- 0.4246, Sum=3.8933 +/- 0.1068 Interval 2, DeltaF=1.9442 +/- 0.2527, Sum=5.0450 +/- 0.1133 Interval 3, DeltaF=3.3355 +/- 0.3178, Sum=7.0207 +/- 0.1281 Interval 4, DeltaF=3.3250 +/- 0.3661, Sum=8.9902 +/- 0.1507 Interval 5, DeltaF=1.0191 +/- 0.3634, Sum=9.5939 +/- 0.1698 Interval 6, DeltaF=-0.7446 +/- 0.2404, Sum=9.1528 +/- 0.1732 Interval 7, DeltaF=-1.5262 +/- 0.3156, Sum=8.2488 +/- 0.1830 Interval 8, DeltaF=-2.4218 +/- 0.3316, Sum=6.8143 +/- 0.1942 Interval 9, DeltaF=-2.9964 +/- 0.4610, Sum=5.0395 +/- 0.2315 Interval 10, DeltaF=-1.0819 +/- 0.1948, Sum=4.3986 +/- 0.2325 Unopt. BAR free energy: 4.3986 +/- 0.2325 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6003 +/- 0.3087, Sum=3.9096 +/- 0.0565 Interval 2, DeltaF=1.9255 +/- 0.1912, Sum=5.0502 +/- 0.0605 Interval 3, DeltaF=3.1839 +/- 0.2466, Sum=6.9361 +/- 0.0704 Interval 4, DeltaF=3.3855 +/- 0.2914, Sum=8.9415 +/- 0.0865 Interval 5, DeltaF=1.0331 +/- 0.3356, Sum=9.5535 +/- 0.1092 Interval 6, DeltaF=-0.7947 +/- 0.2809, Sum=9.0827 +/- 0.1188 Interval 7, DeltaF=-1.6232 +/- 0.2966, Sum=8.1213 +/- 0.1298 Interval 8, DeltaF=-2.3123 +/- 0.2669, Sum=6.7516 +/- 0.1364 Interval 9, DeltaF=-2.9749 +/- 0.2088, Sum=4.9894 +/- 0.1389 Interval 10, DeltaF=-1.0858 +/- 0.1376, Sum=4.3463 +/- 0.1393 Postopt. BAR free energy: 4.3463 +/- 0.1393 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 854 N_k = [354 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.49811419] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.7735301] relative max_delta = 2.671851e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9469 relative max_delta = 3.504572e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5164 relative max_delta = 2.408492e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5987 relative max_delta = 1.247718e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5991 relative max_delta = 5.646438e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5991 relative max_delta = 1.165128e-09 Converged to tolerance of 1.165128e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5991 Final dimensionless free energies f_k = [ 0. 6.59906271] Computing normalized weights... Interval 1, DeltaF=6.5991 +/- 0.3033, Sum=3.9089 +/- 0.0545 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.52158269] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82774178] relative max_delta = 1.675067e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8376 relative max_delta = 5.344516e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9260 relative max_delta = 4.589608e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9260 relative max_delta = 3.010045e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9260 relative max_delta = 2.536743e-11 Converged to tolerance of 2.536743e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9260 Final dimensionless free energies f_k = [ 0. 1.9260145] Computing normalized weights... Interval 2, DeltaF=1.9260 +/- 0.1906, Sum=5.0497 +/- 0.0586 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.60994705] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.41006919] relative max_delta = 3.319914e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4902 relative max_delta = 3.216859e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2034 relative max_delta = 2.226581e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1787 relative max_delta = 7.783863e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1787 relative max_delta = 5.353685e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1787 relative max_delta = 2.608913e-12 Converged to tolerance of 2.608913e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1787 Final dimensionless free energies f_k = [ 0. 3.1786885] Computing normalized weights... Interval 3, DeltaF=3.1787 +/- 0.2450, Sum=6.9326 +/- 0.0685 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.96866839] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.70902157] relative max_delta = 4.332029e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9205 relative max_delta = 1.101114e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7208 relative max_delta = 4.838533e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4029 relative max_delta = 9.343781e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3909 relative max_delta = 3.540554e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3908 relative max_delta = 5.228807e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3908 relative max_delta = 1.140935e-11 Converged to tolerance of 1.140935e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3908 Final dimensionless free energies f_k = [ 0. 3.39084095] Computing normalized weights... Interval 4, DeltaF=3.3908 +/- 0.2799, Sum=8.9411 +/- 0.0828 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 867 N_k = [500 367] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.25593885] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.45295454] relative max_delta = 4.349569e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5153 relative max_delta = 1.209918e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.0676 relative max_delta = 5.173437e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0334 relative max_delta = 3.312556e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0333 relative max_delta = 1.467491e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0333 relative max_delta = 2.854169e-09 Converged to tolerance of 2.854169e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0333 Final dimensionless free energies f_k = [ 0. 1.03325334] Computing normalized weights... Interval 5, DeltaF=1.0333 +/- 0.3346, Sum=9.5531 +/- 0.1061 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 546 N_k = [367 179] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.48715042] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.66919797] relative max_delta = 2.720384e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.6806 relative max_delta = 1.676639e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.7836 relative max_delta = 1.314508e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.7850 relative max_delta = 1.728238e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.7850 relative max_delta = 3.052311e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.7850 relative max_delta = 7.496029e-15 Converged to tolerance of 7.496029e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.7850 Final dimensionless free energies f_k = [ 0. -0.78497323] Computing normalized weights... Interval 6, DeltaF=-0.7850 +/- 0.2710, Sum=9.0882 +/- 0.1146 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 390 N_k = [179 211] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.03078118] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.37661349] relative max_delta = 2.512196e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3992 relative max_delta = 1.614449e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6026 relative max_delta = 1.269031e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6031 relative max_delta = 3.220909e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6031 relative max_delta = 3.590623e-09 Converged to tolerance of 3.590623e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6031 Final dimensionless free energies f_k = [ 0. -1.60309091] Computing normalized weights... Interval 7, DeltaF=-1.6031 +/- 0.2919, Sum=8.1386 +/- 0.1253 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 405 N_k = [211 194] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.59064368] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.05932811] relative max_delta = 2.275909e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0831 relative max_delta = 1.142480e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2972 relative max_delta = 9.320705e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2972 relative max_delta = 1.109379e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2972 relative max_delta = 2.898964e-12 Converged to tolerance of 2.898964e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2972 Final dimensionless free energies f_k = [ 0. -2.29722157] Computing normalized weights... Interval 8, DeltaF=-2.2972 +/- 0.2668, Sum=6.7779 +/- 0.1322 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 694 N_k = [194 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.49283274] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.87232292] relative max_delta = 1.321196e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8828 relative max_delta = 3.623291e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9764 relative max_delta = 3.146102e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9749 relative max_delta = 4.983371e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9749 relative max_delta = 1.228711e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9749 relative max_delta = 5.821818e-15 Converged to tolerance of 5.821818e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9749 Final dimensionless free energies f_k = [ 0. -2.97492601] Computing normalized weights... Interval 9, DeltaF=-2.9749 +/- 0.2109, Sum=5.0157 +/- 0.1348 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 985 N_k = [500 485] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99944451] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07896367] relative max_delta = 7.369957e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0797 relative max_delta = 6.448403e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0859 relative max_delta = 5.770087e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0859 relative max_delta = 6.994768e-08 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0859 relative max_delta = 2.453699e-15 Converged to tolerance of 2.453699e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0859 Final dimensionless free energies f_k = [ 0. -1.08592584] Computing normalized weights... Interval 10, DeltaF=-1.0859 +/- 0.1372, Sum=4.3725 +/- 0.1352 Pairwise MBAR free energy: 4.3725 +/- 0.1352 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4290 N_k = [354 500 500 500 500 367 179 211 194 500 485] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.05303935 2.14728989 2.03816339 1.82235076 1.95923179 1.95861179 1.99447438 1.9997252 1.34174922 0.77429025] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.05960041 3.54635992 3.66472836 3.35053509 3.55363234 3.54152477 3.50271204 3.3205032 2.16899937 1.42643815] relative max_delta = 4.438433e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2983 3.9108 4.4902 4.7648 5.0698 4.9940 4.8385 4.4782 3.1058 2.3240 relative max_delta = 2.990560e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5875 7.3512 11.5740 16.7732 17.9604 17.3035 16.0358 13.9603 10.6427 9.5199 relative max_delta = 7.177252e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5448 8.5666 11.7622 15.6782 16.7483 16.0171 14.3489 12.0763 9.1142 8.0284 relative max_delta = 1.124921e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5964 8.5164 11.7058 15.1510 16.2209 15.4801 13.8020 11.4993 8.5722 7.4865 relative max_delta = 3.557168e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5953 8.5166 11.6985 15.1076 16.1783 15.4375 13.7594 11.4563 8.5296 7.4439 relative max_delta = 2.686331e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.5953 8.5166 11.6985 15.1073 16.1781 15.4372 13.7592 11.4561 8.5293 7.4436 relative max_delta = 1.595980e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.5953 8.5166 11.6985 15.1073 16.1781 15.4372 13.7592 11.4561 8.5293 7.4436 relative max_delta = 5.776072e-10 Converged to tolerance of 5.776072e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5953 8.5166 11.6985 15.1073 16.1781 15.4372 13.7592 11.4561 8.5293 7.4436 Final dimensionless free energies f_k = [ 0. 6.5953492 8.51661546 11.69846219 15.1073157 16.17808446 15.43723001 13.75916565 11.456053 8.52934668 7.44362339] Computing normalized weights... DeltaMij: [[ 0.00000000e+00 3.90667163e+00 5.04470939e+00 6.92943603e+00 8.94862727e+00 9.58288360e+00 9.14404784e+00 8.15006765e+00 6.78584802e+00 5.05225057e+00 4.40913611e+00] [ -3.90667163e+00 0.00000000e+00 1.13803776e+00 3.02276440e+00 5.04195564e+00 5.67621196e+00 5.23737620e+00 4.24339602e+00 2.87917638e+00 1.14557893e+00 5.02464479e-01] [ -5.04470939e+00 -1.13803776e+00 0.00000000e+00 1.88472664e+00 3.90391788e+00 4.53817420e+00 4.09933844e+00 3.10535826e+00 1.74113862e+00 7.54117537e-03 -6.35573278e-01] [ -6.92943603e+00 -3.02276440e+00 -1.88472664e+00 0.00000000e+00 2.01919124e+00 2.65344757e+00 2.21461180e+00 1.22063162e+00 -1.43588016e-01 -1.87718546e+00 -2.52029992e+00] [ -8.94862727e+00 -5.04195564e+00 -3.90391788e+00 -2.01919124e+00 0.00000000e+00 6.34256323e-01 1.95420562e-01 -7.98559622e-01 -2.16277926e+00 -3.89637671e+00 -4.53949116e+00] [ -9.58288360e+00 -5.67621196e+00 -4.53817420e+00 -2.65344757e+00 -6.34256323e-01 0.00000000e+00 -4.38835761e-01 -1.43281595e+00 -2.79703558e+00 -4.53063303e+00 -5.17374748e+00] [ -9.14404784e+00 -5.23737620e+00 -4.09933844e+00 -2.21461180e+00 -1.95420562e-01 4.38835761e-01 0.00000000e+00 -9.93980184e-01 -2.35819982e+00 -4.09179727e+00 -4.73491172e+00] [ -8.15006765e+00 -4.24339602e+00 -3.10535826e+00 -1.22063162e+00 7.98559622e-01 1.43281595e+00 9.93980184e-01 0.00000000e+00 -1.36421964e+00 -3.09781708e+00 -3.74093154e+00] [ -6.78584802e+00 -2.87917638e+00 -1.74113862e+00 1.43588016e-01 2.16277926e+00 2.79703558e+00 2.35819982e+00 1.36421964e+00 0.00000000e+00 -1.73359745e+00 -2.37671190e+00] [ -5.05225057e+00 -1.14557893e+00 -7.54117537e-03 1.87718546e+00 3.89637671e+00 4.53063303e+00 4.09179727e+00 3.09781708e+00 1.73359745e+00 0.00000000e+00 -6.43114454e-01] [ -4.40913611e+00 -5.02464479e-01 6.35573278e-01 2.52029992e+00 4.53949116e+00 5.17374748e+00 4.73491172e+00 3.74093154e+00 2.37671190e+00 6.43114454e-01 0.00000000e+00]] dDeltaMij: [[ 0. 0.05338886 0.06465143 0.07620454 0.09203226 0.1175479 0.12961221 0.14471459 0.15609515 0.16195753 0.16364382] [ 0.05338886 0. 0.02068594 0.04438899 0.06810567 0.09993074 0.11387698 0.13080884 0.14329807 0.14966256 0.15148578] [ 0.06465143 0.02068594 0. 0.03243628 0.06119594 0.09535636 0.10988471 0.12734848 0.14014642 0.14664776 0.14850799] [ 0.07620454 0.04438899 0.03243628 0. 0.04528781 0.08597811 0.10185356 0.12048702 0.13394217 0.14073042 0.14266783] [ 0.09203226 0.06810567 0.06119594 0.04528781 0. 0.0644698 0.08446429 0.10619698 0.12124832 0.12870782 0.1308234 ] [ 0.1175479 0.09993074 0.09535636 0.08597811 0.0644698 0. 0.03928159 0.07485379 0.0950303 0.10437869 0.10697636] [ 0.12961221 0.11387698 0.10988471 0.10185356 0.08446429 0.03928159 0. 0.04759968 0.07453688 0.08623266 0.08936229] [ 0.14471459 0.13080884 0.12734848 0.12048702 0.10619698 0.07485379 0.04759968 0. 0.03679488 0.05477059 0.05959796] [ 0.15609515 0.14329807 0.14014642 0.13394217 0.12124832 0.0950303 0.07453688 0.03679488 0. 0.02291893 0.0307993 ] [ 0.16195753 0.14966256 0.14664776 0.14073042 0.12870782 0.10437869 0.08623266 0.05477059 0.02291893 0. 0.01041858] [ 0.16364382 0.15148578 0.14850799 0.14266783 0.1308234 0.10697636 0.08936229 0.05959796 0.0307993 0.01041858 0. ]] Replica 10 / 40 Computing statistical inefficiencies: lambda 0: g = 2.709 lambda 1: g = 1.659 lambda 2: g = 1.924 lambda 3: g = 1.974 lambda 4: g = 1.917 lambda 5: g = 1.993 lambda 6: g = 1.779 lambda 7: g = 1.076 lambda 8: g = 1.368 lambda 9: g = 1.364 lambda 10: g = 2.757 Subsampling data to produce uncorrelated samples... number of samples per lambda: [411 386 500 476 500 332 386 191 176 324 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.3110 +/- 0.6834, Sum=3.7383 +/- 0.2767 Interval 2, DeltaF=2.0593 +/- 0.2628, Sum=4.9580 +/- 0.2797 Interval 3, DeltaF=3.4701 +/- 0.3383, Sum=7.0135 +/- 0.2878 Interval 4, DeltaF=3.7109 +/- 0.4787, Sum=9.2116 +/- 0.3182 Interval 5, DeltaF=1.6741 +/- 0.6480, Sum=10.2032 +/- 0.4038 Interval 6, DeltaF=-0.5609 +/- 0.3459, Sum=9.8710 +/- 0.4100 Interval 7, DeltaF=-1.4842 +/- 0.3734, Sum=8.9918 +/- 0.4183 Interval 8, DeltaF=-2.3425 +/- 0.3631, Sum=7.6043 +/- 0.4255 Interval 9, DeltaF=-2.8930 +/- 0.2934, Sum=5.8906 +/- 0.4285 Interval 10, DeltaF=-1.0526 +/- 0.1841, Sum=5.2671 +/- 0.4290 Forward EXP free energy: 5.2671 +/- 0.4290 Reverse EXP: Interval 1, DeltaF=8.2142 +/- 0.8152, Sum=4.8656 +/- 0.3936 Interval 2, DeltaF=1.8873 +/- 0.2561, Sum=5.9835 +/- 0.3955 Interval 3, DeltaF=3.2968 +/- 0.4180, Sum=7.9363 +/- 0.4088 Interval 4, DeltaF=3.5814 +/- 0.3733, Sum=10.0577 +/- 0.4171 Interval 5, DeltaF=0.8173 +/- 0.4747, Sum=10.5418 +/- 0.4379 Interval 6, DeltaF=-0.6231 +/- 0.2857, Sum=10.1727 +/- 0.4406 Interval 7, DeltaF=-1.9134 +/- 0.3804, Sum=9.0393 +/- 0.4489 Interval 8, DeltaF=-2.2513 +/- 0.3875, Sum=7.7058 +/- 0.4576 Interval 9, DeltaF=-2.9674 +/- 0.2829, Sum=5.9481 +/- 0.4600 Interval 10, DeltaF=-1.0972 +/- 0.1960, Sum=5.2982 +/- 0.4606 Reverse EXP free energy: 5.2982 +/- 0.4606 Averge of forward and reverse EXP: Interval 1, DeltaF=7.2626 +/- 0.4420, Sum=4.3019 +/- 0.1157 Interval 2, DeltaF=1.9733 +/- 0.0518, Sum=5.4708 +/- 0.1157 Interval 3, DeltaF=3.3835 +/- 0.1137, Sum=7.4749 +/- 0.1160 Interval 4, DeltaF=3.6461 +/- 0.1459, Sum=9.6346 +/- 0.1167 Interval 5, DeltaF=1.2457 +/- 0.2593, Sum=10.3725 +/- 0.1233 Interval 6, DeltaF=-0.5920 +/- 0.0788, Sum=10.0218 +/- 0.1234 Interval 7, DeltaF=-1.6988 +/- 0.1094, Sum=9.0156 +/- 0.1236 Interval 8, DeltaF=-2.2969 +/- 0.1088, Sum=7.6551 +/- 0.1238 Interval 9, DeltaF=-2.9302 +/- 0.0640, Sum=5.9194 +/- 0.1238 Interval 10, DeltaF=-1.0749 +/- 0.0279, Sum=5.2827 +/- 0.1238 Average EXP free energy: 5.2827 +/- 0.1238 Interval 1, DeltaF=8.2142 +/- 0.5114, Sum=4.8656 +/- 0.1549 Interval 2, DeltaF=2.0593 +/- 0.5111, Sum=6.0854 +/- 0.2190 Interval 3, DeltaF=3.2968 +/- 0.7391, Sum=8.0382 +/- 0.3907 Interval 4, DeltaF=3.7109 +/- 0.5574, Sum=10.2363 +/- 0.4319 Interval 5, DeltaF=0.8173 +/- 0.7858, Sum=10.7204 +/- 0.5660 Interval 6, DeltaF=-0.5609 +/- 0.7478, Sum=10.3881 +/- 0.6558 Interval 7, DeltaF=-1.9134 +/- 0.8172, Sum=9.2548 +/- 0.7658 Interval 8, DeltaF=-2.3425 +/- 0.7752, Sum=7.8672 +/- 0.8445 Interval 9, DeltaF=-2.9674 +/- 0.8431, Sum=6.1095 +/- 0.9436 Interval 10, DeltaF=-1.0526 +/- 0.7879, Sum=5.4860 +/- 1.0127 Double-Wide EXP free energy: 5.4860 +/- 1.0127 Method: BAR Interval 1, DeltaF=6.8495 +/- 0.3083, Sum=4.0572 +/- 0.0563 Interval 2, DeltaF=2.0029 +/- 0.1998, Sum=5.2436 +/- 0.0611 Interval 3, DeltaF=3.3356 +/- 0.2453, Sum=7.2194 +/- 0.0707 Interval 4, DeltaF=3.3844 +/- 0.2900, Sum=9.2241 +/- 0.0865 Interval 5, DeltaF=0.9964 +/- 0.3389, Sum=9.8143 +/- 0.1100 Interval 6, DeltaF=-0.6343 +/- 0.2371, Sum=9.4386 +/- 0.1150 Interval 7, DeltaF=-1.7091 +/- 0.2789, Sum=8.4262 +/- 0.1238 Interval 8, DeltaF=-2.3339 +/- 0.2676, Sum=7.0437 +/- 0.1309 Interval 9, DeltaF=-2.9026 +/- 0.2268, Sum=5.3244 +/- 0.1344 Interval 10, DeltaF=-1.0825 +/- 0.1432, Sum=4.6832 +/- 0.1350 BAR free energy: 4.6832 +/- 0.1350 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.3926 +/- 0.5045, Sum=3.7865 +/- 0.1508 Interval 2, DeltaF=2.0354 +/- 0.2449, Sum=4.9922 +/- 0.1549 Interval 3, DeltaF=3.3141 +/- 0.3304, Sum=6.9553 +/- 0.1679 Interval 4, DeltaF=3.2070 +/- 0.3704, Sum=8.8549 +/- 0.1865 Interval 5, DeltaF=1.0288 +/- 0.3731, Sum=9.4643 +/- 0.2039 Interval 6, DeltaF=-0.6238 +/- 0.2373, Sum=9.0948 +/- 0.2066 Interval 7, DeltaF=-1.7748 +/- 0.2364, Sum=8.0435 +/- 0.2093 Interval 8, DeltaF=-2.2984 +/- 0.3421, Sum=6.6821 +/- 0.2204 Interval 9, DeltaF=-2.9384 +/- 0.4448, Sum=4.9416 +/- 0.2497 Interval 10, DeltaF=-1.0953 +/- 0.2389, Sum=4.2928 +/- 0.2519 Unopt. BAR free energy: 4.2928 +/- 0.2519 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8574 +/- 0.3085, Sum=4.0619 +/- 0.0564 Interval 2, DeltaF=2.0030 +/- 0.1997, Sum=5.2483 +/- 0.0611 Interval 3, DeltaF=3.3336 +/- 0.2488, Sum=7.2230 +/- 0.0713 Interval 4, DeltaF=3.3638 +/- 0.3020, Sum=9.2155 +/- 0.0894 Interval 5, DeltaF=0.9963 +/- 0.3388, Sum=9.8056 +/- 0.1123 Interval 6, DeltaF=-0.6426 +/- 0.2426, Sum=9.4250 +/- 0.1176 Interval 7, DeltaF=-1.6989 +/- 0.2904, Sum=8.4187 +/- 0.1278 Interval 8, DeltaF=-2.3323 +/- 0.2673, Sum=7.0372 +/- 0.1346 Interval 9, DeltaF=-2.9022 +/- 0.2213, Sum=5.3181 +/- 0.1377 Interval 10, DeltaF=-1.0837 +/- 0.1507, Sum=4.6762 +/- 0.1384 Postopt. BAR free energy: 4.6762 +/- 0.1384 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 797 N_k = [411 386] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.70838439] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.99975754] relative max_delta = 2.582872e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1845 relative max_delta = 3.562586e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8419 relative max_delta = 2.422528e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8495 relative max_delta = 1.101419e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8495 relative max_delta = 4.409502e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8495 relative max_delta = 2.593418e-16 Converged to tolerance of 2.593418e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8495 Final dimensionless free energies f_k = [ 0. 6.84948116] Computing normalized weights... Interval 1, DeltaF=6.8495 +/- 0.3083, Sum=4.0572 +/- 0.0563 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 886 N_k = [386 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.54264599] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.88611343] relative max_delta = 1.821033e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8977 relative max_delta = 6.121046e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 2.0024 relative max_delta = 5.226546e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 2.0029 relative max_delta = 2.650360e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 2.0029 relative max_delta = 7.956506e-09 Converged to tolerance of 7.956506e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 2.0029 Final dimensionless free energies f_k = [ 0. 2.00291595] Computing normalized weights... Interval 2, DeltaF=2.0029 +/- 0.1998, Sum=5.2436 +/- 0.0611 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 976 N_k = [500 476] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.70375317] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.54537043] relative max_delta = 3.306463e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6283 relative max_delta = 3.153500e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3649 relative max_delta = 2.189267e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 8.782151e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 7.770228e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 6.300797e-12 Converged to tolerance of 6.300797e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3356 Final dimensionless free energies f_k = [ 0. 3.33560414] Computing normalized weights... Interval 3, DeltaF=3.3356 +/- 0.2453, Sum=7.2194 +/- 0.0707 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 976 N_k = [476 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.88101949] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.57220069] relative max_delta = 4.396266e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8032 relative max_delta = 1.281255e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7714 relative max_delta = 5.218637e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4020 relative max_delta = 1.085686e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3844 relative max_delta = 5.207625e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3844 relative max_delta = 1.214971e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3844 relative max_delta = 6.612664e-11 Converged to tolerance of 6.612664e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3844 Final dimensionless free energies f_k = [ 0. 3.38437636] Computing normalized weights... Interval 4, DeltaF=3.3844 +/- 0.2900, Sum=9.2241 +/- 0.0865 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 832 N_k = [500 332] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.2441931] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.43353603] relative max_delta = 4.367409e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.4948 relative max_delta = 1.238894e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.0362 relative max_delta = 5.224394e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 0.9966 relative max_delta = 3.969442e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 0.9964 relative max_delta = 2.440355e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 0.9964 relative max_delta = 9.137596e-09 Converged to tolerance of 9.137596e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 0.9964 Final dimensionless free energies f_k = [ 0. 0.99638234] Computing normalized weights... Interval 5, DeltaF=0.9964 +/- 0.3389, Sum=9.8143 +/- 0.1100 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 718 N_k = [332 386] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.42053124] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.55882476] relative max_delta = 2.474721e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5664 relative max_delta = 1.330675e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.6342 relative max_delta = 1.069884e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.6343 relative max_delta = 1.916413e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.6343 relative max_delta = 7.091904e-10 Converged to tolerance of 7.091904e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.6343 Final dimensionless free energies f_k = [ 0. -0.6343364] Computing normalized weights... Interval 6, DeltaF=-0.6343 +/- 0.2371, Sum=9.4386 +/- 0.1150 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 577 N_k = [386 191] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.02679184] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.41972932] relative max_delta = 2.767693e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4478 relative max_delta = 1.935521e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7016 relative max_delta = 1.491592e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7091 relative max_delta = 4.411931e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7091 relative max_delta = 4.028684e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7091 relative max_delta = 3.359965e-12 Converged to tolerance of 3.359965e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7091 Final dimensionless free energies f_k = [ 0. -1.70910046] Computing normalized weights... Interval 7, DeltaF=-1.7091 +/- 0.2789, Sum=8.4262 +/- 0.1238 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 367 N_k = [191 176] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.6831077] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.12864169] relative max_delta = 2.093044e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1492 relative max_delta = 9.543483e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3337 relative max_delta = 7.909676e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3339 relative max_delta = 8.440063e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3339 relative max_delta = 2.660253e-10 Converged to tolerance of 2.660253e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3339 Final dimensionless free energies f_k = [ 0. -2.33394064] Computing normalized weights... Interval 8, DeltaF=-2.3339 +/- 0.2676, Sum=7.0437 +/- 0.1309 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 500 N_k = [176 324] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.30051243] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.76246445] relative max_delta = 1.672246e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7767 relative max_delta = 5.140020e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9047 relative max_delta = 4.404406e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9026 relative max_delta = 7.097154e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9026 relative max_delta = 1.736178e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9026 relative max_delta = 1.055676e-14 Converged to tolerance of 1.055676e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9026 Final dimensionless free energies f_k = [ 0. -2.90260989] Computing normalized weights... Interval 9, DeltaF=-2.9026 +/- 0.2268, Sum=5.3244 +/- 0.1344 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 824 N_k = [324 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00695297] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07678965] relative max_delta = 6.485638e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0774 relative max_delta = 5.344156e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0825 relative max_delta = 4.786156e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0825 relative max_delta = 2.395268e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0825 relative max_delta = 5.933939e-13 Converged to tolerance of 5.933939e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0825 Final dimensionless free energies f_k = [ 0. -1.08254406] Computing normalized weights... Interval 10, DeltaF=-1.0825 +/- 0.1432, Sum=4.6832 +/- 0.1350 Pairwise MBAR free energy: 4.6832 +/- 0.1350 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4182 N_k = [411 386 500 476 500 332 386 191 176 324 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.99532002 2.02393672 1.925237 1.62687961 1.76921283 1.71000732 1.64418624 1.58305371 1.1107709 0.67656564] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.9464751 3.36696958 3.48700617 3.02839421 3.19954504 3.09892873 2.92879713 2.70091134 1.82113201 1.21249381] relative max_delta = 4.478825e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1957 3.7538 4.3893 4.4826 4.7475 4.5950 4.3134 3.9336 2.8235 2.1582 relative max_delta = 3.260531e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5930 7.4106 12.0852 16.8653 17.9444 17.3229 15.9863 14.1216 10.9038 9.7473 relative max_delta = 7.354343e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7933 8.8987 12.2258 16.0329 17.0151 16.3716 14.6881 12.3961 9.4261 8.3500 relative max_delta = 1.014086e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8235 8.8152 12.2058 15.6106 16.5930 15.9454 14.2487 11.9132 8.9814 7.9030 relative max_delta = 2.910041e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8224 8.8151 12.2005 15.5822 16.5651 15.9175 14.2207 11.8848 8.9535 7.8751 relative max_delta = 1.715071e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8224 8.8151 12.2005 15.5821 16.5650 15.9174 14.2206 11.8847 8.9534 7.8750 relative max_delta = 6.621826e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8224 8.8151 12.2005 15.5821 16.5650 15.9174 14.2206 11.8847 8.9534 7.8750 relative max_delta = 1.050462e-10 Converged to tolerance of 1.050462e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8224 8.8151 12.2005 15.5821 16.5650 15.9174 14.2206 11.8847 8.9534 7.8750 Final dimensionless free energies f_k = [ 0. 6.82240523 8.81512669 12.20052499 15.58210922 16.56502425 15.91740117 14.22062375 11.88471533 8.95335403 7.87497661] Computing normalized weights... DeltaMij: [[ 0. 4.0411654 5.22152874 7.22682658 9.2298652 9.81208248 9.42847115 8.42340651 7.03976072 5.30340596 4.66464274] [-4.0411654 0. 1.18036334 3.18566118 5.1886998 5.77091708 5.38730574 4.38224111 2.99859532 1.26224055 0.62347734] [-5.22152874 -1.18036334 0. 2.00529784 4.00833647 4.59055375 4.20694241 3.20187778 1.81823198 0.08187722 -0.556886 ] [-7.22682658 -3.18566118 -2.00529784 0. 2.00303862 2.5852559 2.20164457 1.19657993 -0.18706586 -1.92342062 -2.56218384] [-9.2298652 -5.1886998 -4.00833647 -2.00303862 0. 0.58221728 0.19860594 -0.80645869 -2.19010448 -3.92645925 -4.56522246] [-9.81208248 -5.77091708 -4.59055375 -2.5852559 -0.58221728 0. -0.38361134 -1.38867597 -2.77232176 -4.50867653 -5.14743974] [-9.42847115 -5.38730574 -4.20694241 -2.20164457 -0.19860594 0.38361134 0. -1.00506463 -2.38871042 -4.12506519 -4.76382841] [-8.42340651 -4.38224111 -3.20187778 -1.19657993 0.80645869 1.38867597 1.00506463 0. -1.38364579 -3.12000056 -3.75876377] [-7.03976072 -2.99859532 -1.81823198 0.18706586 2.19010448 2.77232176 2.38871042 1.38364579 0. -1.73635477 -2.37511798] [-5.30340596 -1.26224055 -0.08187722 1.92342062 3.92645925 4.50867653 4.12506519 3.12000056 1.73635477 0. -0.63876322] [-4.66464274 -0.62347734 0.556886 2.56218384 4.56522246 5.14743974 4.76382841 3.75876377 2.37511798 0.63876322 0. ]] dDeltaMij: [[ 0. 0.0552452 0.06819356 0.07965681 0.09702662 0.12213267 0.13170189 0.14287323 0.15453334 0.1613876 0.16343469] [ 0.0552452 0. 0.0221072 0.04571129 0.07187326 0.10328637 0.11444244 0.12713947 0.14011509 0.14764025 0.14987523] [ 0.06819356 0.0221072 0. 0.03271352 0.06465245 0.09839856 0.11005123 0.12320165 0.13655197 0.14426311 0.1465496 ] [ 0.07965681 0.04571129 0.03271352 0. 0.04927209 0.08901841 0.10175165 0.11584802 0.12995598 0.13803609 0.14042401] [ 0.09702662 0.07187326 0.06465245 0.04927209 0. 0.0654724 0.08191763 0.09888467 0.11509102 0.12414245 0.12679231] [ 0.12213267 0.10328637 0.09839856 0.08901841 0.0654724 0. 0.0327987 0.06393117 0.08695377 0.0986192 0.10193452] [ 0.13170189 0.11444244 0.11005123 0.10175165 0.08191763 0.0327987 0. 0.04277399 0.07227666 0.08601327 0.08979726] [ 0.14287323 0.12713947 0.12320165 0.11584802 0.09888467 0.06393117 0.04277399 0. 0.03849398 0.05808863 0.06356555] [ 0.15453334 0.14011509 0.13655197 0.12995598 0.11509102 0.08695377 0.07227666 0.03849398 0. 0.02472757 0.03343144] [ 0.1613876 0.14764025 0.14426311 0.13803609 0.12414245 0.0986192 0.08601327 0.05808863 0.02472757 0. 0.0112423 ] [ 0.16343469 0.14987523 0.1465496 0.14042401 0.12679231 0.10193452 0.08979726 0.06356555 0.03343144 0.0112423 0. ]] Replica 11 / 40 Computing statistical inefficiencies: lambda 0: g = 1.491 lambda 1: g = 1.950 lambda 2: g = 1.944 lambda 3: g = 1.416 lambda 4: g = 2.351 lambda 5: g = 2.808 lambda 6: g = 1.370 lambda 7: g = 2.287 lambda 8: g = 1.128 lambda 9: g = 1.474 lambda 10: g = 1.446 Subsampling data to produce uncorrelated samples... number of samples per lambda: [441 500 500 262 500 429 413 356 231 500 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.5591 +/- 0.5026, Sum=3.8852 +/- 0.1497 Interval 2, DeltaF=2.0442 +/- 0.2631, Sum=5.0961 +/- 0.1552 Interval 3, DeltaF=3.3401 +/- 0.3708, Sum=7.0746 +/- 0.1752 Interval 4, DeltaF=3.0862 +/- 0.8093, Sum=8.9027 +/- 0.4257 Interval 5, DeltaF=2.1733 +/- 0.4200, Sum=10.1900 +/- 0.4383 Interval 6, DeltaF=-0.2758 +/- 0.2912, Sum=10.0266 +/- 0.4412 Interval 7, DeltaF=-1.5756 +/- 0.3659, Sum=9.0933 +/- 0.4483 Interval 8, DeltaF=-2.3540 +/- 0.2943, Sum=7.6990 +/- 0.4512 Interval 9, DeltaF=-2.9945 +/- 0.2870, Sum=5.9252 +/- 0.4538 Interval 10, DeltaF=-1.0625 +/- 0.1635, Sum=5.2959 +/- 0.4541 Forward EXP free energy: 5.2959 +/- 0.4541 Reverse EXP: Interval 1, DeltaF=6.0938 +/- 0.4025, Sum=3.6096 +/- 0.0960 Interval 2, DeltaF=1.8918 +/- 0.2738, Sum=4.7302 +/- 0.1057 Interval 3, DeltaF=3.0054 +/- 0.3511, Sum=6.5104 +/- 0.1285 Interval 4, DeltaF=3.4212 +/- 0.3912, Sum=8.5369 +/- 0.1573 Interval 5, DeltaF=1.2426 +/- 0.4693, Sum=9.2729 +/- 0.2043 Interval 6, DeltaF=-0.5521 +/- 0.2799, Sum=8.9458 +/- 0.2095 Interval 7, DeltaF=-1.8807 +/- 0.3394, Sum=7.8318 +/- 0.2203 Interval 8, DeltaF=-2.3104 +/- 0.3793, Sum=6.4633 +/- 0.2362 Interval 9, DeltaF=-2.7834 +/- 0.3323, Sum=4.8146 +/- 0.2451 Interval 10, DeltaF=-1.0126 +/- 0.1811, Sum=4.2148 +/- 0.2459 Reverse EXP free energy: 4.2148 +/- 0.2459 Averge of forward and reverse EXP: Interval 1, DeltaF=6.3264 +/- 0.1633, Sum=3.7474 +/- 0.0158 Interval 2, DeltaF=1.9680 +/- 0.0555, Sum=4.9131 +/- 0.0159 Interval 3, DeltaF=3.1727 +/- 0.1005, Sum=6.7925 +/- 0.0170 Interval 4, DeltaF=3.2537 +/- 0.3660, Sum=8.7198 +/- 0.0812 Interval 5, DeltaF=1.7079 +/- 0.1536, Sum=9.7314 +/- 0.0824 Interval 6, DeltaF=-0.4139 +/- 0.0628, Sum=9.4862 +/- 0.0824 Interval 7, DeltaF=-1.7281 +/- 0.0961, Sum=8.4626 +/- 0.0826 Interval 8, DeltaF=-2.3322 +/- 0.0914, Sum=7.0812 +/- 0.0827 Interval 9, DeltaF=-2.8890 +/- 0.0750, Sum=5.3699 +/- 0.0828 Interval 10, DeltaF=-1.0376 +/- 0.0230, Sum=4.7553 +/- 0.0828 Average EXP free energy: 4.7553 +/- 0.0828 Interval 1, DeltaF=6.0938 +/- 0.1247, Sum=3.6096 +/- 0.0092 Interval 2, DeltaF=2.0442 +/- 0.2801, Sum=4.8205 +/- 0.0474 Interval 3, DeltaF=3.0054 +/- 0.2162, Sum=6.6006 +/- 0.0549 Interval 4, DeltaF=3.0862 +/- 0.5982, Sum=8.4287 +/- 0.2189 Interval 5, DeltaF=1.2426 +/- 0.3350, Sum=9.1648 +/- 0.2288 Interval 6, DeltaF=-0.2758 +/- 0.8081, Sum=9.0014 +/- 0.4494 Interval 7, DeltaF=-1.8807 +/- 0.3951, Sum=7.8874 +/- 0.4588 Interval 8, DeltaF=-2.3540 +/- 0.8264, Sum=6.4931 +/- 0.6117 Interval 9, DeltaF=-2.7834 +/- 0.4423, Sum=4.8443 +/- 0.6226 Interval 10, DeltaF=-1.0625 +/- 0.8342, Sum=4.2150 +/- 0.7466 Double-Wide EXP free energy: 4.2150 +/- 0.7466 Method: BAR Interval 1, DeltaF=6.5865 +/- 0.2847, Sum=3.9014 +/- 0.0480 Interval 2, DeltaF=1.9986 +/- 0.1917, Sum=5.0852 +/- 0.0527 Interval 3, DeltaF=3.2372 +/- 0.2657, Sum=7.0027 +/- 0.0673 Interval 4, DeltaF=3.4272 +/- 0.2912, Sum=9.0328 +/- 0.0840 Interval 5, DeltaF=1.2328 +/- 0.3170, Sum=9.7630 +/- 0.1029 Interval 6, DeltaF=-0.5426 +/- 0.2312, Sum=9.4416 +/- 0.1077 Interval 7, DeltaF=-1.7718 +/- 0.2583, Sum=8.3921 +/- 0.1147 Interval 8, DeltaF=-2.4414 +/- 0.2384, Sum=6.9460 +/- 0.1195 Interval 9, DeltaF=-2.9508 +/- 0.2081, Sum=5.1981 +/- 0.1223 Interval 10, DeltaF=-1.0461 +/- 0.1375, Sum=4.5785 +/- 0.1228 BAR free energy: 4.5785 +/- 0.1228 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.5491 +/- 0.4597, Sum=3.8793 +/- 0.1252 Interval 2, DeltaF=2.0357 +/- 0.2579, Sum=5.0851 +/- 0.1312 Interval 3, DeltaF=3.2266 +/- 0.4028, Sum=6.9963 +/- 0.1626 Interval 4, DeltaF=3.3481 +/- 0.3554, Sum=8.9795 +/- 0.1790 Interval 5, DeltaF=1.2778 +/- 0.3484, Sum=9.7364 +/- 0.1929 Interval 6, DeltaF=-0.5444 +/- 0.2255, Sum=9.4140 +/- 0.1953 Interval 7, DeltaF=-1.7958 +/- 0.2560, Sum=8.3503 +/- 0.1991 Interval 8, DeltaF=-2.4112 +/- 0.2798, Sum=6.9220 +/- 0.2044 Interval 9, DeltaF=-2.8429 +/- 0.4282, Sum=5.2381 +/- 0.2315 Interval 10, DeltaF=-1.0335 +/- 0.1941, Sum=4.6259 +/- 0.2325 Unopt. BAR free energy: 4.6259 +/- 0.2325 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.5735 +/- 0.2887, Sum=3.8937 +/- 0.0494 Interval 2, DeltaF=1.9985 +/- 0.1917, Sum=5.0775 +/- 0.0540 Interval 3, DeltaF=3.2382 +/- 0.2729, Sum=6.9956 +/- 0.0697 Interval 4, DeltaF=3.4208 +/- 0.2966, Sum=9.0219 +/- 0.0870 Interval 5, DeltaF=1.2398 +/- 0.3234, Sum=9.7563 +/- 0.1068 Interval 6, DeltaF=-0.5399 +/- 0.2416, Sum=9.4365 +/- 0.1123 Interval 7, DeltaF=-1.7717 +/- 0.2625, Sum=8.3870 +/- 0.1195 Interval 8, DeltaF=-2.4439 +/- 0.2324, Sum=6.9395 +/- 0.1237 Interval 9, DeltaF=-2.9518 +/- 0.2049, Sum=5.1910 +/- 0.1262 Interval 10, DeltaF=-1.0456 +/- 0.1379, Sum=4.5716 +/- 0.1267 Postopt. BAR free energy: 4.5716 +/- 0.1267 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 941 N_k = [441 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.66543589] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.96260419] relative max_delta = 2.613886e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1228 relative max_delta = 3.126966e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5607 relative max_delta = 2.191735e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5865 relative max_delta = 3.905715e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5865 relative max_delta = 3.781817e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5865 relative max_delta = 3.572008e-12 Converged to tolerance of 3.572008e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5865 Final dimensionless free energies f_k = [ 0. 6.58648041] Computing normalized weights... Interval 1, DeltaF=6.5865 +/- 0.2847, Sum=3.9014 +/- 0.0480 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.5535067] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.88773164] relative max_delta = 1.770511e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8988 relative max_delta = 5.838547e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9986 relative max_delta = 4.991709e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9986 relative max_delta = 6.122266e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9986 relative max_delta = 5.011802e-13 Converged to tolerance of 5.011802e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9986 Final dimensionless free energies f_k = [ 0. 1.99856909] Computing normalized weights... Interval 2, DeltaF=1.9986 +/- 0.1917, Sum=5.0852 +/- 0.0527 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 762 N_k = [500 262] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.68668818] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.50609299] relative max_delta = 3.269650e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5863 relative max_delta = 3.100046e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2917 relative max_delta = 2.143007e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2374 relative max_delta = 1.675091e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2372 relative max_delta = 9.121796e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2372 relative max_delta = 2.733892e-09 Converged to tolerance of 2.733892e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2372 Final dimensionless free energies f_k = [ 0. 3.23715181] Computing normalized weights... Interval 3, DeltaF=3.2372 +/- 0.2657, Sum=7.0027 +/- 0.0673 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 762 N_k = [262 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.13160944] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.95530719] relative max_delta = 4.212626e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.1196 relative max_delta = 7.751748e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5570 relative max_delta = 4.040960e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4277 relative max_delta = 3.770929e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4272 relative max_delta = 1.567791e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4272 relative max_delta = 3.126746e-09 Converged to tolerance of 3.126746e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4272 Final dimensionless free energies f_k = [ 0. 3.42717856] Computing normalized weights... Interval 4, DeltaF=3.4272 +/- 0.2912, Sum=9.0328 +/- 0.0840 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 929 N_k = [500 429] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.32823967] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.57598334] relative max_delta = 4.301230e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6470 relative max_delta = 1.097329e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2752 relative max_delta = 4.926321e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2330 relative max_delta = 3.419451e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2328 relative max_delta = 1.793648e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2328 relative max_delta = 4.891391e-09 Converged to tolerance of 4.891391e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2328 Final dimensionless free energies f_k = [ 0. 1.2327825] Computing normalized weights... Interval 5, DeltaF=1.2328 +/- 0.3170, Sum=9.7630 +/- 0.1029 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 842 N_k = [429 413] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.3490202] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.47112891] relative max_delta = 2.591832e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4782 relative max_delta = 1.488572e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5424 relative max_delta = 1.182257e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5426 relative max_delta = 4.151440e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5426 relative max_delta = 5.435283e-09 Converged to tolerance of 5.435283e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5426 Final dimensionless free energies f_k = [ 0. -0.5425953] Computing normalized weights... Interval 6, DeltaF=-0.5426 +/- 0.2312, Sum=9.4416 +/- 0.1077 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 769 N_k = [413 356] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.05610343] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.45630388] relative max_delta = 2.748056e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4873 relative max_delta = 2.086959e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7676 relative max_delta = 1.585341e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7718 relative max_delta = 2.375292e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7718 relative max_delta = 6.187647e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7718 relative max_delta = 4.223399e-14 Converged to tolerance of 4.223399e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7718 Final dimensionless free energies f_k = [ 0. -1.77177267] Computing normalized weights... Interval 7, DeltaF=-1.7718 +/- 0.2583, Sum=8.3921 +/- 0.1147 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 587 N_k = [356 231] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.70621577] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.20783702] relative max_delta = 2.272003e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2310 relative max_delta = 1.036891e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.4395 relative max_delta = 8.548814e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.4414 relative max_delta = 7.551819e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.4414 relative max_delta = 7.502416e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.4414 relative max_delta = 5.457064e-16 Converged to tolerance of 5.457064e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.4414 Final dimensionless free energies f_k = [ 0. -2.44136361] Computing normalized weights... Interval 8, DeltaF=-2.4414 +/- 0.2384, Sum=6.9460 +/- 0.1195 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 731 N_k = [231 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34753071] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.81330738] relative max_delta = 1.655620e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8274 relative max_delta = 4.966725e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9531 relative max_delta = 4.259623e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9508 relative max_delta = 7.988904e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9508 relative max_delta = 2.703209e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9508 relative max_delta = 2.904625e-14 Converged to tolerance of 2.904625e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9508 Final dimensionless free energies f_k = [ 0. -2.95078465] Computing normalized weights... Interval 9, DeltaF=-2.9508 +/- 0.2081, Sum=5.1981 +/- 0.1223 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9600454] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.0389986] relative max_delta = 7.598971e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0397 relative max_delta = 6.822107e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0461 relative max_delta = 6.102374e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0461 relative max_delta = 2.106090e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0461 relative max_delta = 2.334873e-15 Converged to tolerance of 2.334873e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0461 Final dimensionless free energies f_k = [ 0. -1.04609132] Computing normalized weights... Interval 10, DeltaF=-1.0461 +/- 0.1375, Sum=4.5785 +/- 0.1228 Pairwise MBAR free energy: 4.5785 +/- 0.1228 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4632 N_k = [441 500 500 262 500 429 413 356 231 500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.19378819 2.29101309 1.77421298 1.57301647 1.77908189 1.8017215 1.76079115 1.64848556 1.00082273 0.55272786] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.24291679 3.77261319 3.25553976 2.91090585 3.227857 3.23327991 3.0806268 2.74391948 1.62484642 0.99920783] relative max_delta = 3.927252e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.4879 4.1501 4.2667 4.4961 4.9192 4.8717 4.5959 4.0806 2.7477 2.0744 relative max_delta = 3.438234e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7981 7.6690 12.5495 17.3801 18.7243 18.1996 16.7629 14.5458 11.3103 10.2197 relative max_delta = 7.372838e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5450 8.6803 12.0404 15.9448 17.1743 16.6207 14.8871 12.4992 9.5568 8.5040 relative max_delta = 1.191700e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5562 8.5507 11.8519 15.3068 16.5354 15.9783 14.2400 11.8304 8.9111 7.8578 relative max_delta = 4.044610e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5547 8.5512 11.8403 15.2686 16.4980 15.9408 14.2025 11.7927 8.8736 7.8203 relative max_delta = 2.312409e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.5547 8.5512 11.8403 15.2685 16.4978 15.9406 14.2024 11.7926 8.8734 7.8202 relative max_delta = 9.193382e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.5547 8.5512 11.8403 15.2685 16.4978 15.9406 14.2024 11.7926 8.8734 7.8202 relative max_delta = 1.389716e-10 Converged to tolerance of 1.389716e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5547 8.5512 11.8403 15.2685 16.4978 15.9406 14.2024 11.7926 8.8734 7.8202 Final dimensionless free energies f_k = [ 0. 6.55470797 8.55119544 11.8402805 15.2684679 16.49781813 15.94060358 14.20236557 11.79255651 8.87340493 7.82017634] Computing normalized weights... DeltaMij: [[ 0. 3.88259832 5.0651924 7.01344032 9.04408374 9.77227379 9.4422148 8.41259151 6.98517161 5.25604911 4.63218249] [-3.88259832 0. 1.18259409 3.130842 5.16148542 5.88967547 5.55961649 4.5299932 3.1025733 1.3734508 0.74958418] [-5.0651924 -1.18259409 0. 1.94824791 3.97889134 4.70708139 4.3770224 3.34739911 1.91997921 0.19085671 -0.43300991] [-7.01344032 -3.130842 -1.94824791 0. 2.03064342 2.75883347 2.42877449 1.3991512 -0.0282687 -1.7573912 -2.38125782] [-9.04408374 -5.16148542 -3.97889134 -2.03064342 0. 0.72819005 0.39813106 -0.63149223 -2.05891213 -3.78803463 -4.41190125] [-9.77227379 -5.88967547 -4.70708139 -2.75883347 -0.72819005 0. -0.33005899 -1.35968228 -2.78710217 -4.51622467 -5.1400913 ] [-9.4422148 -5.55961649 -4.3770224 -2.42877449 -0.39813106 0.33005899 0. -1.02962329 -2.45704319 -4.18616569 -4.81003231] [-8.41259151 -4.5299932 -3.34739911 -1.3991512 0.63149223 1.35968228 1.02962329 0. -1.4274199 -3.1565424 -3.78040902] [-6.98517161 -3.1025733 -1.91997921 0.0282687 2.05891213 2.78710217 2.45704319 1.4274199 0. -1.7291225 -2.35298912] [-5.25604911 -1.3734508 -0.19085671 1.7573912 3.78803463 4.51622467 4.18616569 3.1565424 1.7291225 0. -0.62386662] [-4.63218249 -0.74958418 0.43300991 2.38125782 4.41190125 5.1400913 4.81003231 3.78040902 2.35298912 0.62386662 0. ]] dDeltaMij: [[ 0. 0.04761985 0.05963433 0.0748371 0.09446569 0.11529209 0.12363332 0.13330267 0.14115902 0.14584782 0.1475578 ] [ 0.04761985 0. 0.02100025 0.04894953 0.07563871 0.10044782 0.10992133 0.12069424 0.12931886 0.1344213 0.13627473] [ 0.05963433 0.02100025 0. 0.03733101 0.06893953 0.09550596 0.10542446 0.11661355 0.12551887 0.13076967 0.13267412] [ 0.0748371 0.04894953 0.03733101 0. 0.04867581 0.08202507 0.09338765 0.1058567 0.11559372 0.121275 0.12332617] [ 0.09446569 0.07563871 0.06893953 0.04867581 0. 0.05649768 0.07196534 0.08754341 0.09909637 0.10566841 0.10801634] [ 0.11529209 0.10044782 0.09550596 0.08202507 0.05649768 0. 0.03063083 0.05804672 0.07435786 0.08291142 0.0858836 ] [ 0.12363332 0.10992133 0.10542446 0.09338765 0.07196534 0.03063083 0. 0.03773764 0.05942855 0.06989876 0.07340171] [ 0.13330267 0.12069424 0.11661355 0.1058567 0.08754341 0.05804672 0.03773764 0. 0.02973407 0.0455634 0.05077624] [ 0.14115902 0.12931886 0.12551887 0.11559372 0.09909637 0.07435786 0.05942855 0.02973407 0. 0.02012499 0.02815249] [ 0.14584782 0.1344213 0.13076967 0.121275 0.10566841 0.08291142 0.06989876 0.0455634 0.02012499 0. 0.01014882] [ 0.1475578 0.13627473 0.13267412 0.12332617 0.10801634 0.0858836 0.07340171 0.05077624 0.02815249 0.01014882 0. ]] Replica 12 / 40 Computing statistical inefficiencies: lambda 0: g = 1.242 lambda 1: g = 1.625 lambda 2: g = 1.593 lambda 3: g = 3.728 lambda 4: g = 1.319 lambda 5: g = 2.049 lambda 6: g = 1.532 lambda 7: g = 2.037 lambda 8: g = 1.822 lambda 9: g = 1.697 lambda 10: g = 1.842 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 500 500 318 500 284 200 173 394 469] Method: EXP Forward EXP: Interval 1, DeltaF=6.7700 +/- 0.4609, Sum=4.0101 +/- 0.1258 Interval 2, DeltaF=1.8971 +/- 0.2747, Sum=5.1338 +/- 0.1335 Interval 3, DeltaF=3.5810 +/- 0.3268, Sum=7.2550 +/- 0.1478 Interval 4, DeltaF=3.6017 +/- 0.5161, Sum=9.3884 +/- 0.2162 Interval 5, DeltaF=1.5547 +/- 0.6924, Sum=10.3093 +/- 0.3569 Interval 6, DeltaF=-0.3525 +/- 0.3536, Sum=10.1005 +/- 0.3645 Interval 7, DeltaF=-1.5279 +/- 0.4443, Sum=9.1955 +/- 0.3828 Interval 8, DeltaF=-2.3499 +/- 0.3410, Sum=7.8036 +/- 0.3889 Interval 9, DeltaF=-2.9421 +/- 0.3151, Sum=6.0608 +/- 0.3934 Interval 10, DeltaF=-1.0889 +/- 0.1711, Sum=5.4158 +/- 0.3937 Forward EXP free energy: 5.4158 +/- 0.3937 Reverse EXP: Interval 1, DeltaF=6.2078 +/- 0.3557, Sum=3.6771 +/- 0.0750 Interval 2, DeltaF=1.8799 +/- 0.2910, Sum=4.7907 +/- 0.0902 Interval 3, DeltaF=3.0315 +/- 0.3072, Sum=6.5863 +/- 0.1061 Interval 4, DeltaF=3.4377 +/- 0.4263, Sum=8.6226 +/- 0.1511 Interval 5, DeltaF=1.1641 +/- 0.4252, Sum=9.3121 +/- 0.1852 Interval 6, DeltaF=-0.4176 +/- 0.2947, Sum=9.0648 +/- 0.1923 Interval 7, DeltaF=-1.9965 +/- 0.3957, Sum=7.8822 +/- 0.2135 Interval 8, DeltaF=-2.2778 +/- 0.3757, Sum=6.5330 +/- 0.2292 Interval 9, DeltaF=-2.8449 +/- 0.3377, Sum=4.8478 +/- 0.2390 Interval 10, DeltaF=-1.1192 +/- 0.1672, Sum=4.1849 +/- 0.2396 Reverse EXP free energy: 4.1849 +/- 0.2396 Averge of forward and reverse EXP: Interval 1, DeltaF=6.4889 +/- 0.1346, Sum=3.8436 +/- 0.0107 Interval 2, DeltaF=1.8885 +/- 0.0617, Sum=4.9622 +/- 0.0110 Interval 3, DeltaF=3.3062 +/- 0.0776, Sum=6.9206 +/- 0.0115 Interval 4, DeltaF=3.5197 +/- 0.1755, Sum=9.0055 +/- 0.0216 Interval 5, DeltaF=1.3594 +/- 0.2789, Sum=9.8107 +/- 0.0509 Interval 6, DeltaF=-0.3851 +/- 0.0829, Sum=9.5826 +/- 0.0510 Interval 7, DeltaF=-1.7622 +/- 0.1371, Sum=8.5388 +/- 0.0522 Interval 8, DeltaF=-2.3138 +/- 0.0995, Sum=7.1683 +/- 0.0526 Interval 9, DeltaF=-2.8935 +/- 0.0823, Sum=5.4543 +/- 0.0527 Interval 10, DeltaF=-1.1041 +/- 0.0220, Sum=4.8004 +/- 0.0527 Average EXP free energy: 4.8004 +/- 0.0527 Interval 1, DeltaF=6.2078 +/- 0.0974, Sum=3.6771 +/- 0.0056 Interval 2, DeltaF=1.8971 +/- 0.2384, Sum=4.8008 +/- 0.0341 Interval 3, DeltaF=3.0315 +/- 0.1809, Sum=6.5965 +/- 0.0393 Interval 4, DeltaF=3.6017 +/- 0.3402, Sum=8.7299 +/- 0.0790 Interval 5, DeltaF=1.1641 +/- 0.3106, Sum=9.4194 +/- 0.0975 Interval 6, DeltaF=-0.3525 +/- 0.6628, Sum=9.2106 +/- 0.2779 Interval 7, DeltaF=-1.9965 +/- 0.3733, Sum=8.0280 +/- 0.2899 Interval 8, DeltaF=-2.3499 +/- 0.7091, Sum=6.6361 +/- 0.4156 Interval 9, DeltaF=-2.8449 +/- 0.4303, Sum=4.9510 +/- 0.4298 Interval 10, DeltaF=-1.0889 +/- 0.7232, Sum=4.3060 +/- 0.5298 Double-Wide EXP free energy: 4.3060 +/- 0.5298 Method: BAR Interval 1, DeltaF=6.7312 +/- 0.2871, Sum=3.9871 +/- 0.0488 Interval 2, DeltaF=1.9116 +/- 0.1955, Sum=5.1195 +/- 0.0538 Interval 3, DeltaF=3.2120 +/- 0.2393, Sum=7.0221 +/- 0.0636 Interval 4, DeltaF=3.3537 +/- 0.3040, Sum=9.0086 +/- 0.0839 Interval 5, DeltaF=1.2878 +/- 0.3152, Sum=9.7714 +/- 0.1025 Interval 6, DeltaF=-0.4145 +/- 0.2360, Sum=9.5259 +/- 0.1077 Interval 7, DeltaF=-1.6990 +/- 0.2908, Sum=8.5195 +/- 0.1188 Interval 8, DeltaF=-2.3454 +/- 0.2643, Sum=7.1302 +/- 0.1258 Interval 9, DeltaF=-2.9083 +/- 0.2277, Sum=5.4076 +/- 0.1295 Interval 10, DeltaF=-1.0939 +/- 0.1416, Sum=4.7596 +/- 0.1300 BAR free energy: 4.7596 +/- 0.1300 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.7379 +/- 0.4527, Sum=3.9911 +/- 0.1214 Interval 2, DeltaF=1.9159 +/- 0.2518, Sum=5.1260 +/- 0.1271 Interval 3, DeltaF=3.3512 +/- 0.3265, Sum=7.1110 +/- 0.1419 Interval 4, DeltaF=3.2633 +/- 0.4171, Sum=9.0440 +/- 0.1753 Interval 5, DeltaF=1.3207 +/- 0.3421, Sum=9.8263 +/- 0.1886 Interval 6, DeltaF=-0.4144 +/- 0.2195, Sum=9.5808 +/- 0.1907 Interval 7, DeltaF=-1.8223 +/- 0.2755, Sum=8.5014 +/- 0.1959 Interval 8, DeltaF=-2.3202 +/- 0.3356, Sum=7.1270 +/- 0.2070 Interval 9, DeltaF=-2.8721 +/- 0.4555, Sum=5.4258 +/- 0.2407 Interval 10, DeltaF=-1.0994 +/- 0.2184, Sum=4.7746 +/- 0.2424 Unopt. BAR free energy: 4.7746 +/- 0.2424 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7266 +/- 0.2878, Sum=3.9844 +/- 0.0491 Interval 2, DeltaF=1.9108 +/- 0.1961, Sum=5.1163 +/- 0.0541 Interval 3, DeltaF=3.2172 +/- 0.2411, Sum=7.0220 +/- 0.0641 Interval 4, DeltaF=3.3524 +/- 0.3171, Sum=9.0077 +/- 0.0875 Interval 5, DeltaF=1.2956 +/- 0.3213, Sum=9.7751 +/- 0.1068 Interval 6, DeltaF=-0.4144 +/- 0.2195, Sum=9.5296 +/- 0.1105 Interval 7, DeltaF=-1.6837 +/- 0.2986, Sum=8.5323 +/- 0.1225 Interval 8, DeltaF=-2.3413 +/- 0.2624, Sum=7.1455 +/- 0.1291 Interval 9, DeltaF=-2.9089 +/- 0.2215, Sum=5.4225 +/- 0.1323 Interval 10, DeltaF=-1.0942 +/- 0.1457, Sum=4.7743 +/- 0.1329 Postopt. BAR free energy: 4.7743 +/- 0.1329 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.51878288] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.84251592] relative max_delta = 2.733565e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0351 relative max_delta = 3.825673e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7534 relative max_delta = 2.544333e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7312 relative max_delta = 3.303444e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7312 relative max_delta = 7.629416e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7312 relative max_delta = 4.024451e-14 Converged to tolerance of 4.024451e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7312 Final dimensionless free energies f_k = [ 0. 6.73121488] Computing normalized weights... Interval 1, DeltaF=6.7312 +/- 0.2871, Sum=3.9871 +/- 0.0488 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.47020407] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.79593756] relative max_delta = 1.813724e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8075 relative max_delta = 6.396755e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9116 relative max_delta = 5.443790e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9116 relative max_delta = 3.105117e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9116 relative max_delta = 2.456090e-11 Converged to tolerance of 2.456090e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9116 Final dimensionless free energies f_k = [ 0. 1.91162042] Computing normalized weights... Interval 2, DeltaF=1.9116 +/- 0.1955, Sum=5.1195 +/- 0.0538 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.63811141] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.4717797] relative max_delta = 3.372745e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5491 relative max_delta = 3.033696e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2369 relative max_delta = 2.124773e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2120 relative max_delta = 7.729702e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2120 relative max_delta = 4.555507e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2120 relative max_delta = 1.657023e-12 Converged to tolerance of 1.657023e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2120 Final dimensionless free energies f_k = [ 0. 3.2120314] Computing normalized weights... Interval 3, DeltaF=3.2120 +/- 0.2393, Sum=7.0221 +/- 0.0636 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 818 N_k = [500 318] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.93119787] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.65186871] relative max_delta = 4.362761e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8757 relative max_delta = 1.193185e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7517 relative max_delta = 5.000429e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3758 relative max_delta = 1.113339e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3538 relative max_delta = 6.569018e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3537 relative max_delta = 2.193193e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3537 relative max_delta = 2.438116e-10 Converged to tolerance of 2.438116e-10 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3537 Final dimensionless free energies f_k = [ 0. 3.35371587] Computing normalized weights... Interval 4, DeltaF=3.3537 +/- 0.3040, Sum=9.0086 +/- 0.0839 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 818 N_k = [318 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.38213817] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.66154442] relative max_delta = 4.223545e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7279 relative max_delta = 9.113866e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3173 relative max_delta = 4.474426e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2879 relative max_delta = 2.284004e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2878 relative max_delta = 5.684413e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2878 relative max_delta = 3.531325e-10 Converged to tolerance of 3.531325e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2878 Final dimensionless free energies f_k = [ 0. 1.28780947] Computing normalized weights... Interval 5, DeltaF=1.2878 +/- 0.3152, Sum=9.7714 +/- 0.1025 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 784 N_k = [500 284] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.27036365] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.36320268] relative max_delta = 2.556122e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.3683 relative max_delta = 1.382658e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4142 relative max_delta = 1.108040e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4145 relative max_delta = 6.661581e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4145 relative max_delta = 2.436893e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4145 relative max_delta = 1.205411e-15 Converged to tolerance of 1.205411e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4145 Final dimensionless free energies f_k = [ 0. -0.41446481] Computing normalized weights... Interval 6, DeltaF=-0.4145 +/- 0.2360, Sum=9.5259 +/- 0.1077 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 484 N_k = [284 200] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99240886] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.38583596] relative max_delta = 2.838915e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4165 relative max_delta = 2.166469e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6938 relative max_delta = 1.637060e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6990 relative max_delta = 3.072497e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6990 relative max_delta = 1.208105e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6990 relative max_delta = 1.855780e-13 Converged to tolerance of 1.855780e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6990 Final dimensionless free energies f_k = [ 0. -1.69903389] Computing normalized weights... Interval 7, DeltaF=-1.6990 +/- 0.2908, Sum=8.5195 +/- 0.1188 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 373 N_k = [200 173] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.71214785] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.15080804] relative max_delta = 2.039513e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1702 relative max_delta = 8.938368e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3449 relative max_delta = 7.449033e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3454 relative max_delta = 2.369376e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3454 relative max_delta = 3.694320e-09 Converged to tolerance of 3.694320e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3454 Final dimensionless free energies f_k = [ 0. -2.34543251] Computing normalized weights... Interval 8, DeltaF=-2.3454 +/- 0.2643, Sum=7.1302 +/- 0.1258 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 567 N_k = [173 394] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.32100863] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.76646933] relative max_delta = 1.610214e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7810 relative max_delta = 5.212639e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9108 relative max_delta = 4.460431e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9083 relative max_delta = 8.670037e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9083 relative max_delta = 3.172136e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9083 relative max_delta = 4.260285e-14 Converged to tolerance of 4.260285e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9083 Final dimensionless free energies f_k = [ 0. -2.90827731] Computing normalized weights... Interval 9, DeltaF=-2.9083 +/- 0.2277, Sum=5.4076 +/- 0.1295 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 863 N_k = [394 469] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01012153] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08727245] relative max_delta = 7.095822e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0879 relative max_delta = 6.109022e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0939 relative max_delta = 5.467727e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0939 relative max_delta = 1.395227e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0939 relative max_delta = 8.768790e-14 Converged to tolerance of 8.768790e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0939 Final dimensionless free energies f_k = [ 0. -1.09391679] Computing normalized weights... Interval 10, DeltaF=-1.0939 +/- 0.1416, Sum=4.7596 +/- 0.1300 Pairwise MBAR free energy: 4.7596 +/- 0.1300 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4338 N_k = [500 500 500 500 318 500 284 200 173 394 469] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.00333967 2.03489366 1.96974773 1.46347895 1.56696039 1.6365051 1.69810418 1.67409434 1.08107474 0.57015459] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.98012333 3.38625872 3.54794475 2.74404873 2.87924788 2.95564496 2.95938015 2.76997956 1.73672356 1.04888296] relative max_delta = 4.448201e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2459 3.7837 4.4431 4.3276 4.5924 4.6281 4.5183 4.1554 2.8976 2.1625 relative max_delta = 3.701706e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7928 7.5347 12.1029 17.5436 18.9443 18.5991 17.3816 15.3431 12.0774 10.9311 relative max_delta = 7.575833e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7179 8.7755 11.9380 16.0794 17.3461 16.9127 15.2456 12.9423 9.9702 8.8774 relative max_delta = 1.384073e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7205 8.6260 11.8572 15.2849 16.5542 16.1113 14.4273 12.0934 9.1535 8.0595 relative max_delta = 5.127876e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7192 8.6258 11.8426 15.1801 16.4534 16.0104 14.3263 11.9921 9.0525 7.9586 relative max_delta = 6.369354e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7192 8.6257 11.8424 15.1785 16.4518 16.0088 14.3247 11.9906 9.0510 7.9570 relative max_delta = 9.991908e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7192 8.6257 11.8424 15.1785 16.4518 16.0088 14.3247 11.9906 9.0510 7.9570 relative max_delta = 2.521087e-08 Newton-Raphson iteration 7 current f_k for states with samples = 0.0000 6.7192 8.6257 11.8424 15.1785 16.4518 16.0088 14.3247 11.9906 9.0510 7.9570 relative max_delta = 7.720093e-15 Converged to tolerance of 7.720093e-15 in 8 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7192 8.6257 11.8424 15.1785 16.4518 16.0088 14.3247 11.9906 9.0510 7.9570 Final dimensionless free energies f_k = [ 0. 6.71920215 8.62573466 11.84244232 15.17848189 16.45181038 16.008828 14.32472252 11.99057196 9.05097948 7.95701707] Computing normalized weights... DeltaMij: [[ 0. 3.98003436 5.10934477 7.01472084 8.99078166 9.74502168 9.48262667 8.4850681 7.10246356 5.36123315 4.71323836] [-3.98003436 0. 1.12931041 3.03468648 5.0107473 5.76498732 5.50259231 4.50503374 3.1224292 1.38119879 0.733204 ] [-5.10934477 -1.12931041 0. 1.90537607 3.8814369 4.63567692 4.3732819 3.37572334 1.9931188 0.25188839 -0.3961064 ] [-7.01472084 -3.03468648 -1.90537607 0. 1.97606082 2.73030084 2.46790583 1.47034726 0.08774272 -1.65348769 -2.30148248] [-8.99078166 -5.0107473 -3.8814369 -1.97606082 0. 0.75424002 0.49184501 -0.50571356 -1.8883181 -3.62954851 -4.2775433 ] [-9.74502168 -5.76498732 -4.63567692 -2.73030084 -0.75424002 0. -0.26239501 -1.25995358 -2.64255812 -4.38378853 -5.03178332] [-9.48262667 -5.50259231 -4.3732819 -2.46790583 -0.49184501 0.26239501 0. -0.99755857 -2.38016311 -4.12139352 -4.76938831] [-8.4850681 -4.50503374 -3.37572334 -1.47034726 0.50571356 1.25995358 0.99755857 0. -1.38260454 -3.12383495 -3.77182974] [-7.10246356 -3.1224292 -1.9931188 -0.08774272 1.8883181 2.64255812 2.38016311 1.38260454 0. -1.74123041 -2.3892252 ] [-5.36123315 -1.38119879 -0.25188839 1.65348769 3.62954851 4.38378853 4.12139352 3.12383495 1.74123041 0. -0.64799479] [-4.71323836 -0.733204 0.3961064 2.30148248 4.2775433 5.03178332 4.76938831 3.77182974 2.3892252 0.64799479 0. ]] dDeltaMij: [[ 0. 0.04811124 0.06071544 0.07244497 0.09416932 0.11751008 0.12587699 0.14002667 0.15170959 0.15851964 0.16050457] [ 0.04811124 0. 0.02147421 0.04404429 0.07460907 0.1025072 0.11200054 0.12769719 0.14040977 0.1477416 0.14986935] [ 0.06071544 0.02147421 0. 0.03143729 0.06815649 0.09791226 0.10781097 0.12403893 0.13709117 0.14459137 0.1467648 ] [ 0.07244497 0.04404429 0.03143729 0. 0.05382939 0.08847482 0.09931931 0.11673373 0.13051857 0.13837548 0.140645 ] [ 0.09416932 0.07460907 0.06815649 0.05382939 0. 0.05710578 0.0727271 0.09514446 0.11162769 0.12072043 0.12331531] [ 0.11751008 0.1025072 0.09791226 0.08847482 0.05710578 0. 0.03253036 0.06907023 0.09046112 0.10146649 0.10454024] [ 0.12587699 0.11200054 0.10781097 0.09931931 0.0727271 0.03253036 0. 0.04723053 0.07447244 0.08758125 0.09112691] [ 0.14002667 0.12769719 0.12403893 0.11673373 0.09514446 0.06907023 0.04723053 0. 0.0374076 0.05707187 0.06238466] [ 0.15170959 0.14040977 0.13709117 0.13051857 0.11162769 0.09046112 0.07447244 0.0374076 0. 0.02458812 0.0329833 ] [ 0.15851964 0.1477416 0.14459137 0.13837548 0.12072043 0.10146649 0.08758125 0.05707187 0.02458812 0. 0.01097139] [ 0.16050457 0.14986935 0.1467648 0.140645 0.12331531 0.10454024 0.09112691 0.06238466 0.0329833 0.01097139 0. ]] Replica 13 / 40 Computing statistical inefficiencies: lambda 0: g = 1.577 lambda 1: g = 1.223 lambda 2: g = 1.330 lambda 3: g = 1.573 lambda 4: g = 1.625 lambda 5: g = 1.490 lambda 6: g = 1.978 lambda 7: g = 1.393 lambda 8: g = 1.779 lambda 9: g = 1.510 lambda 10: g = 1.078 Subsampling data to produce uncorrelated samples... number of samples per lambda: [491 340 430 500 500 500 500 182 313 500 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.9787 +/- 0.4325, Sum=4.1338 +/- 0.1108 Interval 2, DeltaF=1.9250 +/- 0.2724, Sum=5.2740 +/- 0.1192 Interval 3, DeltaF=3.2746 +/- 0.4296, Sum=7.2136 +/- 0.1618 Interval 4, DeltaF=3.7740 +/- 0.4403, Sum=9.4491 +/- 0.1984 Interval 5, DeltaF=1.4815 +/- 0.5223, Sum=10.3267 +/- 0.2559 Interval 6, DeltaF=-0.3559 +/- 0.3533, Sum=10.1159 +/- 0.2663 Interval 7, DeltaF=-1.2958 +/- 0.3867, Sum=9.3483 +/- 0.2807 Interval 8, DeltaF=-2.2515 +/- 0.3642, Sum=8.0147 +/- 0.2915 Interval 9, DeltaF=-2.8469 +/- 0.2520, Sum=6.3283 +/- 0.2939 Interval 10, DeltaF=-1.0821 +/- 0.1620, Sum=5.6874 +/- 0.2943 Forward EXP free energy: 5.6874 +/- 0.2943 Reverse EXP: Interval 1, DeltaF=6.2872 +/- 0.4327, Sum=3.7242 +/- 0.1109 Interval 2, DeltaF=2.1366 +/- 0.3636, Sum=4.9898 +/- 0.1357 Interval 3, DeltaF=3.3119 +/- 0.3164, Sum=6.9515 +/- 0.1481 Interval 4, DeltaF=3.5719 +/- 0.3984, Sum=9.0673 +/- 0.1754 Interval 5, DeltaF=0.9476 +/- 0.4212, Sum=9.6286 +/- 0.2045 Interval 6, DeltaF=-0.4935 +/- 0.2610, Sum=9.3363 +/- 0.2084 Interval 7, DeltaF=-1.4147 +/- 0.4623, Sum=8.4983 +/- 0.2439 Interval 8, DeltaF=-2.3830 +/- 0.3476, Sum=7.0868 +/- 0.2541 Interval 9, DeltaF=-2.8992 +/- 0.2753, Sum=5.3695 +/- 0.2581 Interval 10, DeltaF=-1.0424 +/- 0.2037, Sum=4.7521 +/- 0.2592 Reverse EXP free energy: 4.7521 +/- 0.2592 Averge of forward and reverse EXP: Interval 1, DeltaF=6.6330 +/- 0.1440, Sum=3.9290 +/- 0.0123 Interval 2, DeltaF=2.0308 +/- 0.0825, Sum=5.1319 +/- 0.0129 Interval 3, DeltaF=3.2932 +/- 0.1143, Sum=7.0826 +/- 0.0151 Interval 4, DeltaF=3.6729 +/- 0.1363, Sum=9.2582 +/- 0.0187 Interval 5, DeltaF=1.2145 +/- 0.1771, Sum=9.9776 +/- 0.0263 Interval 6, DeltaF=-0.4247 +/- 0.0774, Sum=9.7261 +/- 0.0266 Interval 7, DeltaF=-1.3552 +/- 0.1420, Sum=8.9233 +/- 0.0291 Interval 8, DeltaF=-2.3173 +/- 0.0976, Sum=7.5507 +/- 0.0297 Interval 9, DeltaF=-2.8731 +/- 0.0538, Sum=5.8489 +/- 0.0297 Interval 10, DeltaF=-1.0622 +/- 0.0267, Sum=5.2197 +/- 0.0297 Average EXP free energy: 5.2197 +/- 0.0297 Interval 1, DeltaF=6.2872 +/- 0.1441, Sum=3.7242 +/- 0.0123 Interval 2, DeltaF=1.9250 +/- 0.2115, Sum=4.8644 +/- 0.0292 Interval 3, DeltaF=3.3119 +/- 0.2610, Sum=6.8262 +/- 0.0498 Interval 4, DeltaF=3.7740 +/- 0.3326, Sum=9.0617 +/- 0.0823 Interval 5, DeltaF=0.9476 +/- 0.3501, Sum=9.6230 +/- 0.1097 Interval 6, DeltaF=-0.3559 +/- 0.4798, Sum=9.4122 +/- 0.1751 Interval 7, DeltaF=-1.4147 +/- 0.4168, Sum=8.5742 +/- 0.2031 Interval 8, DeltaF=-2.2515 +/- 0.5257, Sum=7.2405 +/- 0.2608 Interval 9, DeltaF=-2.8992 +/- 0.4706, Sum=5.5233 +/- 0.2920 Interval 10, DeltaF=-1.0821 +/- 0.5404, Sum=4.8823 +/- 0.3394 Double-Wide EXP free energy: 4.8823 +/- 0.3394 Method: BAR Interval 1, DeltaF=6.7654 +/- 0.3100, Sum=4.0074 +/- 0.0569 Interval 2, DeltaF=1.9425 +/- 0.2090, Sum=5.1580 +/- 0.0625 Interval 3, DeltaF=3.3603 +/- 0.2454, Sum=7.1484 +/- 0.0720 Interval 4, DeltaF=3.4261 +/- 0.2832, Sum=9.1778 +/- 0.0862 Interval 5, DeltaF=1.1780 +/- 0.3097, Sum=9.8756 +/- 0.1033 Interval 6, DeltaF=-0.4575 +/- 0.2150, Sum=9.6046 +/- 0.1069 Interval 7, DeltaF=-1.5398 +/- 0.2748, Sum=8.6925 +/- 0.1158 Interval 8, DeltaF=-2.3392 +/- 0.2479, Sum=7.3069 +/- 0.1214 Interval 9, DeltaF=-2.9210 +/- 0.2024, Sum=5.5767 +/- 0.1238 Interval 10, DeltaF=-1.0747 +/- 0.1375, Sum=4.9401 +/- 0.1243 BAR free energy: 4.9401 +/- 0.1243 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9477 +/- 0.5312, Sum=4.1154 +/- 0.1672 Interval 2, DeltaF=1.9215 +/- 0.2508, Sum=5.2536 +/- 0.1713 Interval 3, DeltaF=3.2703 +/- 0.3228, Sum=7.1907 +/- 0.1821 Interval 4, DeltaF=3.3254 +/- 0.3635, Sum=9.1605 +/- 0.1982 Interval 5, DeltaF=1.1624 +/- 0.3377, Sum=9.8490 +/- 0.2094 Interval 6, DeltaF=-0.4621 +/- 0.2112, Sum=9.5753 +/- 0.2110 Interval 7, DeltaF=-1.6007 +/- 0.2007, Sum=8.6272 +/- 0.2124 Interval 8, DeltaF=-2.3812 +/- 0.3804, Sum=7.2167 +/- 0.2290 Interval 9, DeltaF=-2.9000 +/- 0.3800, Sum=5.4989 +/- 0.2445 Interval 10, DeltaF=-1.0682 +/- 0.1963, Sum=4.8662 +/- 0.2455 Unopt. BAR free energy: 4.8662 +/- 0.2455 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7640 +/- 0.3090, Sum=4.0066 +/- 0.0566 Interval 2, DeltaF=1.9437 +/- 0.2103, Sum=5.1579 +/- 0.0623 Interval 3, DeltaF=3.3525 +/- 0.2474, Sum=7.1437 +/- 0.0721 Interval 4, DeltaF=3.4135 +/- 0.2937, Sum=9.1657 +/- 0.0884 Interval 5, DeltaF=1.1786 +/- 0.3141, Sum=9.8638 +/- 0.1060 Interval 6, DeltaF=-0.4621 +/- 0.2112, Sum=9.5901 +/- 0.1092 Interval 7, DeltaF=-1.5154 +/- 0.2981, Sum=8.6925 +/- 0.1212 Interval 8, DeltaF=-2.3476 +/- 0.2604, Sum=7.3019 +/- 0.1277 Interval 9, DeltaF=-2.9212 +/- 0.1995, Sum=5.5716 +/- 0.1299 Interval 10, DeltaF=-1.0743 +/- 0.1383, Sum=4.9352 +/- 0.1304 Postopt. BAR free energy: 4.9352 +/- 0.1304 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 831 N_k = [491 340] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.66639238] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.92578794] relative max_delta = 2.556739e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1174 relative max_delta = 3.743658e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8191 relative max_delta = 2.495493e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7655 relative max_delta = 7.922449e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7654 relative max_delta = 6.882972e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7654 relative max_delta = 5.071697e-12 Converged to tolerance of 5.071697e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7654 Final dimensionless free energies f_k = [ 0. 6.76540922] Computing normalized weights... Interval 1, DeltaF=6.7654 +/- 0.3100, Sum=4.0074 +/- 0.0569 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 770 N_k = [340 430] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.48675692] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82295826] relative max_delta = 1.844262e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8348 relative max_delta = 6.480585e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9420 relative max_delta = 5.516107e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9425 relative max_delta = 2.555860e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9425 relative max_delta = 6.453716e-09 Converged to tolerance of 6.453716e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9425 Final dimensionless free energies f_k = [ 0. 1.9424668] Computing normalized weights... Interval 2, DeltaF=1.9425 +/- 0.2090, Sum=5.1580 +/- 0.0625 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 930 N_k = [430 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.7269937] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.58280054] relative max_delta = 3.313484e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6630 relative max_delta = 3.011953e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3786 relative max_delta = 2.117954e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3603 relative max_delta = 5.448152e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3603 relative max_delta = 9.090555e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3603 relative max_delta = 2.867850e-14 Converged to tolerance of 2.867850e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3603 Final dimensionless free energies f_k = [ 0. 3.36026551] Computing normalized weights... Interval 3, DeltaF=3.3603 +/- 0.2454, Sum=7.1484 +/- 0.0720 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.00767288] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.7632727] relative max_delta = 4.285212e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9634 relative max_delta = 1.019140e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6861 relative max_delta = 4.673597e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4328 relative max_delta = 7.378706e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4261 relative max_delta = 1.964947e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4261 relative max_delta = 1.395236e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4261 relative max_delta = 7.015066e-13 Converged to tolerance of 7.015066e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4261 Final dimensionless free energies f_k = [ 0. 3.42607019] Computing normalized weights... Interval 4, DeltaF=3.4261 +/- 0.2832, Sum=9.1778 +/- 0.0862 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.31716313] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.55575669] relative max_delta = 4.293130e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6224 relative max_delta = 1.071272e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2135 relative max_delta = 4.870658e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.1781 relative max_delta = 2.999458e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.1780 relative max_delta = 1.196218e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.1780 relative max_delta = 1.892000e-09 Converged to tolerance of 1.892000e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.1780 Final dimensionless free energies f_k = [ 0. 1.17800337] Computing normalized weights... Interval 5, DeltaF=1.1780 +/- 0.3097, Sum=9.8756 +/- 0.1033 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.30516393] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.40516452] relative max_delta = 2.468148e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4104 relative max_delta = 1.271614e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4574 relative max_delta = 1.027370e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4575 relative max_delta = 2.195213e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4575 relative max_delta = 1.060656e-09 Converged to tolerance of 1.060656e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4575 Final dimensionless free energies f_k = [ 0. -0.45747245] Computing normalized weights... Interval 6, DeltaF=-0.4575 +/- 0.2150, Sum=9.6046 +/- 0.1069 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 682 N_k = [500 182] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.92656784] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.28169128] relative max_delta = 2.770741e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3065 relative max_delta = 1.899436e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5316 relative max_delta = 1.469811e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5398 relative max_delta = 5.329488e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5398 relative max_delta = 7.012317e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5398 relative max_delta = 1.213336e-11 Converged to tolerance of 1.213336e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5398 Final dimensionless free energies f_k = [ 0. -1.53984528] Computing normalized weights... Interval 7, DeltaF=-1.5398 +/- 0.2748, Sum=8.6925 +/- 0.1158 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 495 N_k = [182 313] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.74495425] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.16364812] relative max_delta = 1.935129e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1815 relative max_delta = 8.172667e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3414 relative max_delta = 6.828977e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3392 relative max_delta = 9.452731e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3392 relative max_delta = 1.642128e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3392 relative max_delta = 3.986853e-15 Converged to tolerance of 3.986853e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3392 Final dimensionless free energies f_k = [ 0. -2.33915655] Computing normalized weights... Interval 8, DeltaF=-2.3392 +/- 0.2479, Sum=7.3069 +/- 0.1214 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 813 N_k = [313 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.31520184] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.77346878] relative max_delta = 1.652324e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7884 relative max_delta = 5.372393e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9228 relative max_delta = 4.597408e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9210 relative max_delta = 6.101955e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9210 relative max_delta = 9.871659e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9210 relative max_delta = 6.081246e-16 Converged to tolerance of 6.081246e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9210 Final dimensionless free energies f_k = [ 0. -2.92104085] Computing normalized weights... Interval 9, DeltaF=-2.9210 +/- 0.2024, Sum=5.5767 +/- 0.1238 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98573559] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06738613] relative max_delta = 7.649578e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0681 relative max_delta = 6.875581e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0747 relative max_delta = 6.149903e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0747 relative max_delta = 2.544616e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0747 relative max_delta = 1.859446e-15 Converged to tolerance of 1.859446e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0747 Final dimensionless free energies f_k = [ 0. -1.07472973] Computing normalized weights... Interval 10, DeltaF=-1.0747 +/- 0.1375, Sum=4.9401 +/- 0.1243 Pairwise MBAR free energy: 4.9401 +/- 0.1243 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4756 N_k = [491 340 430 500 500 500 500 182 313 500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.86289281 1.84607723 1.76854069 1.47238095 1.53856205 1.55042486 1.57331411 1.56462818 0.94598837 0.4332873 ] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.73197657 3.05100771 3.1913343 2.75412551 2.8356643 2.83342057 2.79101084 2.61339687 1.52389571 0.83282472] relative max_delta = 4.458303e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.9936 3.4400 4.0683 4.2282 4.4359 4.3926 4.2535 3.9160 2.6099 1.8754 relative max_delta = 3.607456e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5210 7.1572 11.6087 16.5918 17.8995 17.4828 16.4114 14.5135 11.2872 10.1752 relative max_delta = 7.521783e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7884 8.8804 12.1312 15.9545 17.1324 16.6836 15.1466 12.8858 9.9571 8.8836 relative max_delta = 1.005795e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8154 8.7609 12.1208 15.5495 16.7276 16.2722 14.7070 12.4135 9.5136 8.4391 relative max_delta = 2.823484e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8139 8.7602 12.1154 15.5283 16.7070 16.2516 14.6863 12.3926 9.4929 8.4184 relative max_delta = 1.269960e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8139 8.7602 12.1154 15.5283 16.7070 16.2516 14.6862 12.3925 9.4929 8.4183 relative max_delta = 2.737428e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8139 8.7602 12.1154 15.5283 16.7070 16.2516 14.6862 12.3925 9.4929 8.4183 relative max_delta = 1.491993e-11 Converged to tolerance of 1.491993e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8139 8.7602 12.1154 15.5283 16.7070 16.2516 14.6862 12.3925 9.4929 8.4183 Final dimensionless free energies f_k = [ 0. 6.81388552 8.76023557 12.1154184 15.52828343 16.70699996 16.25159687 14.68624852 12.39253032 9.49285311 8.41831247] Computing normalized weights... DeltaMij: [[ 0. 4.03611886 5.18901468 7.17641477 9.19798218 9.89618 9.62642774 8.69921346 7.34055851 5.62297141 4.98648086] [-4.03611886 0. 1.15289582 3.14029591 5.16186332 5.86006114 5.59030888 4.6630946 3.30443965 1.58685255 0.950362 ] [-5.18901468 -1.15289582 0. 1.98740009 4.0089675 4.70716532 4.43741306 3.51019878 2.15154383 0.43395673 -0.20253382] [-7.17641477 -3.14029591 -1.98740009 0. 2.02156741 2.71976523 2.45001297 1.52279869 0.16414374 -1.55344336 -2.18993391] [-9.19798218 -5.16186332 -4.0089675 -2.02156741 0. 0.69819782 0.42844556 -0.49876872 -1.85742367 -3.57501077 -4.21150132] [-9.89618 -5.86006114 -4.70716532 -2.71976523 -0.69819782 0. -0.26975226 -1.19696654 -2.55562149 -4.27320859 -4.90969914] [-9.62642774 -5.59030888 -4.43741306 -2.45001297 -0.42844556 0.26975226 0. -0.92721428 -2.28586923 -4.00345633 -4.63994688] [-8.69921346 -4.6630946 -3.51019878 -1.52279869 0.49876872 1.19696654 0.92721428 0. -1.35865495 -3.07624205 -3.7127326 ] [-7.34055851 -3.30443965 -2.15154383 -0.16414374 1.85742367 2.55562149 2.28586923 1.35865495 0. -1.7175871 -2.35407765] [-5.62297141 -1.58685255 -0.43395673 1.55344336 3.57501077 4.27320859 4.00345633 3.07624205 1.7175871 0. -0.63649055] [-4.98648086 -0.950362 0.20253382 2.18993391 4.21150132 4.90969914 4.63994688 3.7127326 2.35407765 0.63649055 0. ]] dDeltaMij: [[ 0. 0.05453078 0.06909486 0.08072085 0.09658091 0.11585629 0.12260246 0.13300733 0.14335802 0.14867101 0.15030726] [ 0.05453078 0. 0.02401456 0.04692277 0.07085645 0.09547549 0.10355796 0.11568854 0.12745356 0.13340149 0.13522264] [ 0.06909486 0.02401456 0. 0.03237412 0.06250352 0.08945297 0.09803322 0.11077048 0.12300679 0.12915967 0.13103978] [ 0.08072085 0.04692277 0.03237412 0. 0.04658326 0.07910454 0.08869244 0.10259595 0.11570005 0.12222131 0.12420649] [ 0.09658091 0.07085645 0.06250352 0.04658326 0. 0.05425247 0.06742324 0.0848874 0.10033144 0.10778659 0.1100325 ] [ 0.11585629 0.09547549 0.08945297 0.07910454 0.05425247 0. 0.02700325 0.05785255 0.07882221 0.08811467 0.09084809] [ 0.12260246 0.10355796 0.09803322 0.08869244 0.06742324 0.02700325 0. 0.04125686 0.06702496 0.07777387 0.08085867] [ 0.13300733 0.11568854 0.11077048 0.10259595 0.0848874 0.05785255 0.04125686 0. 0.0331956 0.04942938 0.05419863] [ 0.14335802 0.12745356 0.12300679 0.11570005 0.10033144 0.07882221 0.06702496 0.0331956 0. 0.02122597 0.02897702] [ 0.14867101 0.13340149 0.12915967 0.12222131 0.10778659 0.08811467 0.07777387 0.04942938 0.02122597 0. 0.01003132] [ 0.15030726 0.13522264 0.13103978 0.12420649 0.1100325 0.09084809 0.08085867 0.05419863 0.02897702 0.01003132 0. ]] Replica 14 / 40 Computing statistical inefficiencies: lambda 0: g = 1.932 lambda 1: g = 2.848 lambda 2: g = 1.464 lambda 3: g = 1.731 lambda 4: g = 1.505 lambda 5: g = 2.160 lambda 6: g = 2.633 lambda 7: g = 1.415 lambda 8: g = 1.746 lambda 9: g = 1.000 lambda 10: g = 2.562 Subsampling data to produce uncorrelated samples... number of samples per lambda: [245 355 323 489 500 409 294 232 170 434 290] Method: EXP Forward EXP: Interval 1, DeltaF=6.9760 +/- 0.5276, Sum=4.1322 +/- 0.1649 Interval 2, DeltaF=1.8386 +/- 0.3431, Sum=5.2213 +/- 0.1790 Interval 3, DeltaF=3.6829 +/- 0.3379, Sum=7.4028 +/- 0.1913 Interval 4, DeltaF=3.6237 +/- 0.4801, Sum=9.5493 +/- 0.2351 Interval 5, DeltaF=2.3189 +/- 0.3698, Sum=10.9228 +/- 0.2486 Interval 6, DeltaF=-0.5509 +/- 0.5035, Sum=10.5965 +/- 0.2905 Interval 7, DeltaF=-1.8290 +/- 0.5686, Sum=9.5131 +/- 0.3479 Interval 8, DeltaF=-2.2654 +/- 0.3374, Sum=8.1712 +/- 0.3544 Interval 9, DeltaF=-2.9829 +/- 0.3234, Sum=6.4043 +/- 0.3598 Interval 10, DeltaF=-1.0619 +/- 0.1698, Sum=5.7753 +/- 0.3602 Forward EXP free energy: 5.7753 +/- 0.3602 Reverse EXP: Interval 1, DeltaF=6.2042 +/- 0.3718, Sum=3.6750 +/- 0.0819 Interval 2, DeltaF=1.9047 +/- 0.2834, Sum=4.8032 +/- 0.0947 Interval 3, DeltaF=3.1676 +/- 0.3328, Sum=6.6795 +/- 0.1152 Interval 4, DeltaF=3.6196 +/- 0.3639, Sum=8.8236 +/- 0.1394 Interval 5, DeltaF=0.8465 +/- 0.4030, Sum=9.3250 +/- 0.1694 Interval 6, DeltaF=-0.6098 +/- 0.3022, Sum=8.9638 +/- 0.1778 Interval 7, DeltaF=-1.3120 +/- 0.3597, Sum=8.1866 +/- 0.1936 Interval 8, DeltaF=-2.2882 +/- 0.3611, Sum=6.8312 +/- 0.2084 Interval 9, DeltaF=-3.0238 +/- 0.2588, Sum=5.0401 +/- 0.2122 Interval 10, DeltaF=-1.0577 +/- 0.1916, Sum=4.4136 +/- 0.2133 Reverse EXP free energy: 4.4136 +/- 0.2133 Averge of forward and reverse EXP: Interval 1, DeltaF=6.5901 +/- 0.1691, Sum=3.9036 +/- 0.0169 Interval 2, DeltaF=1.8717 +/- 0.0775, Sum=5.0122 +/- 0.0173 Interval 3, DeltaF=3.4253 +/- 0.0866, Sum=7.0412 +/- 0.0179 Interval 4, DeltaF=3.6217 +/- 0.1446, Sum=9.1864 +/- 0.0218 Interval 5, DeltaF=1.5827 +/- 0.1156, Sum=10.1239 +/- 0.0231 Interval 6, DeltaF=-0.5804 +/- 0.1467, Sum=9.7801 +/- 0.0264 Interval 7, DeltaF=-1.5705 +/- 0.1895, Sum=8.8499 +/- 0.0339 Interval 8, DeltaF=-2.2768 +/- 0.0942, Sum=7.5012 +/- 0.0343 Interval 9, DeltaF=-3.0034 +/- 0.0676, Sum=5.7222 +/- 0.0344 Interval 10, DeltaF=-1.0598 +/- 0.0254, Sum=5.0945 +/- 0.0344 Average EXP free energy: 5.0945 +/- 0.0344 Interval 1, DeltaF=6.2042 +/- 0.1064, Sum=3.6750 +/- 0.0067 Interval 2, DeltaF=1.8386 +/- 0.3162, Sum=4.7641 +/- 0.0596 Interval 3, DeltaF=3.1676 +/- 0.1938, Sum=6.6404 +/- 0.0636 Interval 4, DeltaF=3.6237 +/- 0.3938, Sum=8.7868 +/- 0.1117 Interval 5, DeltaF=0.8465 +/- 0.2850, Sum=9.2883 +/- 0.1217 Interval 6, DeltaF=-0.5509 +/- 0.4968, Sum=8.9619 +/- 0.1902 Interval 7, DeltaF=-1.3120 +/- 0.3415, Sum=8.1848 +/- 0.2023 Interval 8, DeltaF=-2.2654 +/- 0.6453, Sum=6.8429 +/- 0.3190 Interval 9, DeltaF=-3.0238 +/- 0.3865, Sum=5.0518 +/- 0.3310 Interval 10, DeltaF=-1.0619 +/- 0.6614, Sum=4.4228 +/- 0.4204 Double-Wide EXP free energy: 4.4228 +/- 0.4204 Method: BAR Interval 1, DeltaF=6.7954 +/- 0.3286, Sum=4.0251 +/- 0.0639 Interval 2, DeltaF=1.9798 +/- 0.2149, Sum=5.1978 +/- 0.0696 Interval 3, DeltaF=3.2662 +/- 0.2558, Sum=7.1325 +/- 0.0796 Interval 4, DeltaF=3.4748 +/- 0.2791, Sum=9.1907 +/- 0.0920 Interval 5, DeltaF=1.1608 +/- 0.3277, Sum=9.8783 +/- 0.1119 Interval 6, DeltaF=-0.5619 +/- 0.2398, Sum=9.5455 +/- 0.1169 Interval 7, DeltaF=-1.5378 +/- 0.2777, Sum=8.6346 +/- 0.1255 Interval 8, DeltaF=-2.2592 +/- 0.2705, Sum=7.2964 +/- 0.1328 Interval 9, DeltaF=-2.9261 +/- 0.2214, Sum=5.5631 +/- 0.1360 Interval 10, DeltaF=-1.0540 +/- 0.1440, Sum=4.9388 +/- 0.1365 BAR free energy: 4.9388 +/- 0.1365 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9250 +/- 0.4684, Sum=4.1019 +/- 0.1299 Interval 2, DeltaF=1.9434 +/- 0.2899, Sum=5.2531 +/- 0.1392 Interval 3, DeltaF=3.4256 +/- 0.3085, Sum=7.2822 +/- 0.1501 Interval 4, DeltaF=3.2614 +/- 0.3633, Sum=9.2140 +/- 0.1693 Interval 5, DeltaF=1.2056 +/- 0.3614, Sum=9.9281 +/- 0.1861 Interval 6, DeltaF=-0.5719 +/- 0.2262, Sum=9.5894 +/- 0.1886 Interval 7, DeltaF=-1.4537 +/- 0.2662, Sum=8.7283 +/- 0.1932 Interval 8, DeltaF=-2.2416 +/- 0.3092, Sum=7.4005 +/- 0.2013 Interval 9, DeltaF=-2.9934 +/- 0.4661, Sum=5.6274 +/- 0.2389 Interval 10, DeltaF=-1.0534 +/- 0.1632, Sum=5.0035 +/- 0.2395 Unopt. BAR free energy: 5.0035 +/- 0.2395 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7937 +/- 0.3310, Sum=4.0242 +/- 0.0649 Interval 2, DeltaF=1.9799 +/- 0.2149, Sum=5.1969 +/- 0.0704 Interval 3, DeltaF=3.2717 +/- 0.2539, Sum=7.1349 +/- 0.0801 Interval 4, DeltaF=3.4528 +/- 0.2934, Sum=9.1801 +/- 0.0950 Interval 5, DeltaF=1.1654 +/- 0.3328, Sum=9.8704 +/- 0.1154 Interval 6, DeltaF=-0.5521 +/- 0.2552, Sum=9.5434 +/- 0.1217 Interval 7, DeltaF=-1.5614 +/- 0.2906, Sum=8.6185 +/- 0.1316 Interval 8, DeltaF=-2.2544 +/- 0.2674, Sum=7.2831 +/- 0.1382 Interval 9, DeltaF=-2.9251 +/- 0.2153, Sum=5.5505 +/- 0.1409 Interval 10, DeltaF=-1.0539 +/- 0.1394, Sum=4.9262 +/- 0.1414 Postopt. BAR free energy: 4.9262 +/- 0.1414 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 600 N_k = [245 355] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.44076421] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.82910398] relative max_delta = 2.874943e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0179 relative max_delta = 3.761737e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7212 relative max_delta = 2.534291e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7951 relative max_delta = 1.087640e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7954 relative max_delta = 3.619325e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7954 relative max_delta = 4.037739e-10 Converged to tolerance of 4.037739e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7954 Final dimensionless free energies f_k = [ 0. 6.79536642] Computing normalized weights... Interval 1, DeltaF=6.7954 +/- 0.3286, Sum=4.0251 +/- 0.0639 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 678 N_k = [355 323] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53297236] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.86387547] relative max_delta = 1.775350e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8755 relative max_delta = 6.187551e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9799 relative max_delta = 5.273131e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9798 relative max_delta = 6.020555e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9798 relative max_delta = 2.184530e-11 Converged to tolerance of 2.184530e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9798 Final dimensionless free energies f_k = [ 0. 1.97976266] Computing normalized weights... Interval 2, DeltaF=1.9798 +/- 0.2149, Sum=5.1978 +/- 0.0696 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 812 N_k = [323 489] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.70812216] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.53594924] relative max_delta = 3.264368e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6088 relative max_delta = 2.792469e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2634 relative max_delta = 2.005955e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2662 relative max_delta = 8.338782e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2662 relative max_delta = 7.812003e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2662 relative max_delta = 3.263210e-15 Converged to tolerance of 3.263210e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2662 Final dimensionless free energies f_k = [ 0. 3.26615189] Computing normalized weights... Interval 3, DeltaF=3.2662 +/- 0.2558, Sum=7.1325 +/- 0.0796 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 989 N_k = [489 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.99979897] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.75810981] relative max_delta = 4.313217e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9756 relative max_delta = 1.101097e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8266 relative max_delta = 4.837115e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4882 relative max_delta = 9.703246e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4748 relative max_delta = 3.845295e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4748 relative max_delta = 6.303314e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4748 relative max_delta = 1.695413e-11 Converged to tolerance of 1.695413e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4748 Final dimensionless free energies f_k = [ 0. 3.47478618] Computing normalized weights... Interval 4, DeltaF=3.4748 +/- 0.2791, Sum=9.1907 +/- 0.0920 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 909 N_k = [500 409] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.28333524] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.50368788] relative max_delta = 4.374785e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5755 relative max_delta = 1.247884e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2094 relative max_delta = 5.241506e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.1611 relative max_delta = 4.160419e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.1608 relative max_delta = 2.896924e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.1608 relative max_delta = 1.387769e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.1608 relative max_delta = 5.547379e-15 Converged to tolerance of 5.547379e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.1608 Final dimensionless free energies f_k = [ 0. 1.16078127] Computing normalized weights... Interval 5, DeltaF=1.1608 +/- 0.3277, Sum=9.8783 +/- 0.1119 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 703 N_k = [409 294] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.36799724] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.49288344] relative max_delta = 2.533788e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4997 relative max_delta = 1.372358e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5615 relative max_delta = 1.100594e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5619 relative max_delta = 6.193483e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5619 relative max_delta = 2.022223e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5619 relative max_delta = 9.879310e-16 Converged to tolerance of 9.879310e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5619 Final dimensionless free energies f_k = [ 0. -0.56189298] Computing normalized weights... Interval 6, DeltaF=-0.5619 +/- 0.2398, Sum=9.5455 +/- 0.1169 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 526 N_k = [294 232] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.94528427] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.28972174] relative max_delta = 2.670634e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3141 relative max_delta = 1.856133e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5344 relative max_delta = 1.435479e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5378 relative max_delta = 2.245370e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5378 relative max_delta = 6.066048e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5378 relative max_delta = 4.389424e-14 Converged to tolerance of 4.389424e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5378 Final dimensionless free energies f_k = [ 0. -1.53782282] Computing normalized weights... Interval 7, DeltaF=-1.5378 +/- 0.2777, Sum=8.6346 +/- 0.1255 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 402 N_k = [232 170] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.52884547] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.00684685] relative max_delta = 2.381853e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0319 relative max_delta = 1.233316e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2577 relative max_delta = 1.000156e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2592 relative max_delta = 6.522880e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2592 relative max_delta = 3.770248e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2592 relative max_delta = 1.572563e-15 Converged to tolerance of 1.572563e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2592 Final dimensionless free energies f_k = [ 0. -2.25918706] Computing normalized weights... Interval 8, DeltaF=-2.2592 +/- 0.2705, Sum=7.2964 +/- 0.1328 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 604 N_k = [170 434] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.3788543] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.80270028] relative max_delta = 1.512277e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8153 relative max_delta = 4.481610e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9283 relative max_delta = 3.859173e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9261 relative max_delta = 7.494631e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9261 relative max_delta = 2.774005e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9261 relative max_delta = 3.536162e-14 Converged to tolerance of 3.536162e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9261 Final dimensionless free energies f_k = [ 0. -2.92613279] Computing normalized weights... Interval 9, DeltaF=-2.9261 +/- 0.2214, Sum=5.5631 +/- 0.1360 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 724 N_k = [434 290] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97676998] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.04854119] relative max_delta = 6.844863e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0491 relative max_delta = 5.159964e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0540 relative max_delta = 4.622942e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0540 relative max_delta = 1.899073e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0540 relative max_delta = 3.210719e-13 Converged to tolerance of 3.210719e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0540 Final dimensionless free energies f_k = [ 0. -1.05395689] Computing normalized weights... Interval 10, DeltaF=-1.0540 +/- 0.1440, Sum=4.9388 +/- 0.1365 Pairwise MBAR free energy: 4.9388 +/- 0.1365 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3741 N_k = [245 355 323 489 500 409 294 232 170 434 290] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.95047371 1.98415724 2.02953161 1.86173679 1.92043524 1.90937413 1.92799999 1.89073473 1.23210633 0.71686475] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.93221869 3.32369069 3.633297 3.42286311 3.49540812 3.4578392 3.38751953 3.15864849 2.03484293 1.34969561] relative max_delta = 4.414077e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1886 3.7106 4.4412 4.7817 4.9796 4.8988 4.7233 4.3307 2.9973 2.2716 relative max_delta = 2.980479e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.6410 7.3733 11.4986 16.4978 17.7800 17.3065 16.1252 14.1488 10.9321 9.8494 relative max_delta = 7.199351e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7070 8.7979 11.9971 15.7956 16.9306 16.4161 14.8912 12.6131 9.6537 8.6034 relative max_delta = 9.070688e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7760 8.7591 12.0314 15.5114 16.6424 16.1224 14.5873 12.2801 9.3476 8.2964 relative max_delta = 2.001108e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7752 8.7588 12.0283 15.4954 16.6267 16.1067 14.5716 12.2641 9.3318 8.2807 relative max_delta = 9.638376e-04 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7752 8.7588 12.0283 15.4953 16.6267 16.1067 14.5715 12.2641 9.3318 8.2806 relative max_delta = 1.859369e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7752 8.7588 12.0283 15.4953 16.6267 16.1067 14.5715 12.2641 9.3318 8.2806 relative max_delta = 7.949143e-12 Converged to tolerance of 7.949143e-12 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7752 8.7588 12.0283 15.4953 16.6267 16.1067 14.5715 12.2641 9.3318 8.2806 Final dimensionless free energies f_k = [ 0. 6.77519816 8.75875606 12.02825998 15.49532319 16.62670381 16.10666437 14.5715494 12.26406346 9.33180352 8.28062593] Computing normalized weights... DeltaMij: [[ 0. 4.01320289 5.18813831 7.12478758 9.1784586 9.84861759 9.54057881 8.63127288 7.26446279 5.52757572 4.90492398] [-4.01320289 0. 1.17493542 3.11158469 5.16525571 5.8354147 5.52737592 4.61807 3.2512599 1.51437283 0.89172109] [-5.18813831 -1.17493542 0. 1.93664927 3.99032029 4.66047928 4.3524405 3.44313457 2.07632448 0.33943741 -0.28321433] [-7.12478758 -3.11158469 -1.93664927 0. 2.05367102 2.72383001 2.41579123 1.5064853 0.13967521 -1.59721186 -2.2198636 ] [-9.1784586 -5.16525571 -3.99032029 -2.05367102 0. 0.67015899 0.36212021 -0.54718572 -1.91399581 -3.65088288 -4.27353462] [-9.84861759 -5.8354147 -4.66047928 -2.72383001 -0.67015899 0. -0.30803878 -1.21734471 -2.5841548 -4.32104187 -4.94369361] [-9.54057881 -5.52737592 -4.3524405 -2.41579123 -0.36212021 0.30803878 0. -0.90930593 -2.27611602 -4.01300309 -4.63565483] [-8.63127288 -4.61807 -3.44313457 -1.5064853 0.54718572 1.21734471 0.90930593 0. -1.3668101 -3.10369716 -3.72634891] [-7.26446279 -3.2512599 -2.07632448 -0.13967521 1.91399581 2.5841548 2.27611602 1.3668101 0. -1.73688707 -2.35953881] [-5.52757572 -1.51437283 -0.33943741 1.59721186 3.65088288 4.32104187 4.01300309 3.10369716 1.73688707 0. -0.62265174] [-4.90492398 -0.89172109 0.28321433 2.2198636 4.27353462 4.94369361 4.63565483 3.72634891 2.35953881 0.62265174 0. ]] dDeltaMij: [[ 0. 0.06297177 0.07698237 0.08890263 0.10257879 0.12454023 0.13301228 0.14473524 0.1559099 0.16223847 0.16422672] [ 0.06297177 0. 0.02549277 0.05020183 0.07181843 0.1007301 0.11103395 0.12483815 0.13763782 0.14476738 0.14699214] [ 0.07698237 0.02549277 0. 0.034428 0.06233023 0.09420432 0.10514955 0.11963467 0.1329363 0.14030497 0.14259936] [ 0.08890263 0.05020183 0.034428 0. 0.04575077 0.08412177 0.09622139 0.11186855 0.12599277 0.13374455 0.13614954] [ 0.10257879 0.07181843 0.06233023 0.04575077 0. 0.06182155 0.07745181 0.09620457 0.11231606 0.12094761 0.12360186] [ 0.12454023 0.1007301 0.09420432 0.08412177 0.06182155 0. 0.03183442 0.06481845 0.08698019 0.09786944 0.10113107] [ 0.13301228 0.11103395 0.10514955 0.09622139 0.07745181 0.03183442 0. 0.04363021 0.07196295 0.08487888 0.0886218 ] [ 0.14473524 0.12483815 0.11963467 0.11186855 0.09620457 0.06481845 0.04363021 0. 0.03826867 0.05709475 0.0625389 ] [ 0.1559099 0.13763782 0.1329363 0.12599277 0.11231606 0.08698019 0.07196295 0.03826867 0. 0.02389839 0.03277181] [ 0.16223847 0.14476738 0.14030497 0.13374455 0.12094761 0.09786944 0.08487888 0.05709475 0.02389839 0. 0.01164876] [ 0.16422672 0.14699214 0.14259936 0.13614954 0.12360186 0.10113107 0.0886218 0.0625389 0.03277181 0.01164876 0. ]] Replica 15 / 40 Computing statistical inefficiencies: lambda 0: g = 2.339 lambda 1: g = 2.380 lambda 2: g = 1.650 lambda 3: g = 1.996 lambda 4: g = 1.040 lambda 5: g = 1.115 lambda 6: g = 1.915 lambda 7: g = 2.875 lambda 8: g = 1.254 lambda 9: g = 1.317 lambda 10: g = 3.053 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 480 500 312 381 392 426 193 246 405 420] Method: EXP Forward EXP: Interval 1, DeltaF=6.6941 +/- 0.4889, Sum=3.9652 +/- 0.1416 Interval 2, DeltaF=1.9970 +/- 0.2596, Sum=5.1481 +/- 0.1471 Interval 3, DeltaF=3.0799 +/- 0.3951, Sum=6.9724 +/- 0.1737 Interval 4, DeltaF=4.0023 +/- 0.4252, Sum=9.3431 +/- 0.2041 Interval 5, DeltaF=1.8418 +/- 0.6557, Sum=10.4341 +/- 0.3264 Interval 6, DeltaF=-0.8060 +/- 0.6291, Sum=9.9567 +/- 0.4018 Interval 7, DeltaF=-1.5402 +/- 0.3453, Sum=9.0443 +/- 0.4080 Interval 8, DeltaF=-2.2633 +/- 0.3346, Sum=7.7037 +/- 0.4134 Interval 9, DeltaF=-2.8862 +/- 0.2576, Sum=5.9941 +/- 0.4152 Interval 10, DeltaF=-1.0401 +/- 0.1783, Sum=5.3780 +/- 0.4156 Forward EXP free energy: 5.3780 +/- 0.4156 Reverse EXP: Interval 1, DeltaF=7.0612 +/- 0.5232, Sum=4.1826 +/- 0.1622 Interval 2, DeltaF=1.9074 +/- 0.2908, Sum=5.3124 +/- 0.1697 Interval 3, DeltaF=3.3488 +/- 0.4189, Sum=7.2961 +/- 0.1990 Interval 4, DeltaF=3.4057 +/- 0.3888, Sum=9.3134 +/- 0.2183 Interval 5, DeltaF=1.3801 +/- 0.4170, Sum=10.1309 +/- 0.2413 Interval 6, DeltaF=-0.5173 +/- 0.2924, Sum=9.8245 +/- 0.2466 Interval 7, DeltaF=-1.6790 +/- 0.3727, Sum=8.8299 +/- 0.2600 Interval 8, DeltaF=-2.3641 +/- 0.3618, Sum=7.4296 +/- 0.2713 Interval 9, DeltaF=-2.7637 +/- 0.2855, Sum=5.7926 +/- 0.2755 Interval 10, DeltaF=-1.0606 +/- 0.1828, Sum=5.1643 +/- 0.2762 Reverse EXP free energy: 5.1643 +/- 0.2762 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8777 +/- 0.1978, Sum=4.0739 +/- 0.0232 Interval 2, DeltaF=1.9522 +/- 0.0589, Sum=5.2303 +/- 0.0233 Interval 3, DeltaF=3.2144 +/- 0.1278, Sum=7.1342 +/- 0.0252 Interval 4, DeltaF=3.7040 +/- 0.1283, Sum=9.3283 +/- 0.0270 Interval 5, DeltaF=1.6110 +/- 0.2524, Sum=10.2825 +/- 0.0464 Interval 6, DeltaF=-0.6617 +/- 0.2203, Sum=9.8906 +/- 0.0546 Interval 7, DeltaF=-1.6096 +/- 0.0996, Sum=8.9371 +/- 0.0549 Interval 8, DeltaF=-2.3137 +/- 0.0937, Sum=7.5666 +/- 0.0552 Interval 9, DeltaF=-2.8249 +/- 0.0572, Sum=5.8933 +/- 0.0552 Interval 10, DeltaF=-1.0503 +/- 0.0251, Sum=5.2712 +/- 0.0552 Average EXP free energy: 5.2712 +/- 0.0552 Interval 1, DeltaF=7.0612 +/- 0.2107, Sum=4.1826 +/- 0.0263 Interval 2, DeltaF=1.9970 +/- 0.2653, Sum=5.3655 +/- 0.0493 Interval 3, DeltaF=3.3488 +/- 0.3399, Sum=7.3492 +/- 0.0843 Interval 4, DeltaF=4.0023 +/- 0.3483, Sum=9.7199 +/- 0.1108 Interval 5, DeltaF=1.3801 +/- 0.4228, Sum=10.5374 +/- 0.1532 Interval 6, DeltaF=-0.8060 +/- 0.6726, Sum=10.0599 +/- 0.3087 Interval 7, DeltaF=-1.6790 +/- 0.4656, Sum=9.0654 +/- 0.3343 Interval 8, DeltaF=-2.2633 +/- 0.7546, Sum=7.7247 +/- 0.4749 Interval 9, DeltaF=-2.7637 +/- 0.5024, Sum=6.0877 +/- 0.4979 Interval 10, DeltaF=-1.0401 +/- 0.7634, Sum=5.4716 +/- 0.6059 Double-Wide EXP free energy: 5.4716 +/- 0.6059 Method: BAR Interval 1, DeltaF=6.8135 +/- 0.2915, Sum=4.0359 +/- 0.0503 Interval 2, DeltaF=1.9744 +/- 0.1956, Sum=5.2054 +/- 0.0552 Interval 3, DeltaF=3.1421 +/- 0.2689, Sum=7.0666 +/- 0.0699 Interval 4, DeltaF=3.4139 +/- 0.3011, Sum=9.0888 +/- 0.0881 Interval 5, DeltaF=1.4572 +/- 0.3249, Sum=9.9519 +/- 0.1081 Interval 6, DeltaF=-0.5935 +/- 0.2327, Sum=9.6004 +/- 0.1127 Interval 7, DeltaF=-1.6898 +/- 0.2779, Sum=8.5994 +/- 0.1216 Interval 8, DeltaF=-2.3821 +/- 0.2604, Sum=7.1884 +/- 0.1281 Interval 9, DeltaF=-2.8878 +/- 0.2121, Sum=5.4778 +/- 0.1308 Interval 10, DeltaF=-1.0419 +/- 0.1460, Sum=4.8607 +/- 0.1315 BAR free energy: 4.8607 +/- 0.1315 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.6775 +/- 0.4717, Sum=3.9553 +/- 0.1318 Interval 2, DeltaF=1.9895 +/- 0.2542, Sum=5.1338 +/- 0.1372 Interval 3, DeltaF=3.0076 +/- 0.3641, Sum=6.9153 +/- 0.1581 Interval 4, DeltaF=3.4488 +/- 0.3825, Sum=8.9582 +/- 0.1803 Interval 5, DeltaF=1.4392 +/- 0.3722, Sum=9.8107 +/- 0.1981 Interval 6, DeltaF=-0.5803 +/- 0.2312, Sum=9.4669 +/- 0.2006 Interval 7, DeltaF=-1.6523 +/- 0.2257, Sum=8.4882 +/- 0.2029 Interval 8, DeltaF=-2.3749 +/- 0.3606, Sum=7.0814 +/- 0.2170 Interval 9, DeltaF=-2.7774 +/- 0.4025, Sum=5.4363 +/- 0.2373 Interval 10, DeltaF=-1.0463 +/- 0.2069, Sum=4.8165 +/- 0.2386 Unopt. BAR free energy: 4.8165 +/- 0.2386 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8166 +/- 0.2922, Sum=4.0377 +/- 0.0506 Interval 2, DeltaF=1.9741 +/- 0.1958, Sum=5.2070 +/- 0.0554 Interval 3, DeltaF=3.1336 +/- 0.2720, Sum=7.0632 +/- 0.0707 Interval 4, DeltaF=3.4108 +/- 0.3103, Sum=9.0835 +/- 0.0908 Interval 5, DeltaF=1.4513 +/- 0.3401, Sum=9.9432 +/- 0.1138 Interval 6, DeltaF=-0.6011 +/- 0.2392, Sum=9.5871 +/- 0.1187 Interval 7, DeltaF=-1.6959 +/- 0.2914, Sum=8.5826 +/- 0.1289 Interval 8, DeltaF=-2.3836 +/- 0.2684, Sum=7.1707 +/- 0.1358 Interval 9, DeltaF=-2.8917 +/- 0.2072, Sum=5.4578 +/- 0.1382 Interval 10, DeltaF=-1.0421 +/- 0.1466, Sum=4.8406 +/- 0.1387 Postopt. BAR free energy: 4.8406 +/- 0.1387 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 980 N_k = [500 480] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.64365347] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.94289633] relative max_delta = 2.628505e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1326 relative max_delta = 3.696129e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8270 relative max_delta = 2.481933e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8135 relative max_delta = 1.988872e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8135 relative max_delta = 4.274816e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8135 relative max_delta = 1.929270e-14 Converged to tolerance of 1.929270e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8135 Final dimensionless free energies f_k = [ 0. 6.81347786] Computing normalized weights... Interval 1, DeltaF=6.8135 +/- 0.2915, Sum=4.0359 +/- 0.0503 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 980 N_k = [480 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.51918006] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.8564043] relative max_delta = 1.816545e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8682 relative max_delta = 6.306578e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9742 relative max_delta = 5.371823e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9744 relative max_delta = 6.206881e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9744 relative max_delta = 1.456072e-10 Converged to tolerance of 1.456072e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9744 Final dimensionless free energies f_k = [ 0. 1.97436132] Computing normalized weights... Interval 2, DeltaF=1.9744 +/- 0.1956, Sum=5.2054 +/- 0.0552 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 812 N_k = [500 312] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.57873867] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.34731133] relative max_delta = 3.274268e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4331 relative max_delta = 3.527524e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1916 relative max_delta = 2.376343e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1423 relative max_delta = 1.567264e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1421 relative max_delta = 6.107779e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1421 relative max_delta = 9.365615e-10 Converged to tolerance of 9.365615e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1421 Final dimensionless free energies f_k = [ 0. 3.14212628] Computing normalized weights... Interval 3, DeltaF=3.1421 +/- 0.2689, Sum=7.0666 +/- 0.0699 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 693 N_k = [312 381] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.08034165] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.8714726] relative max_delta = 4.227318e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0521 relative max_delta = 8.803557e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6150 relative max_delta = 4.323218e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4170 relative max_delta = 5.793272e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4139 relative max_delta = 8.987098e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4139 relative max_delta = 2.241034e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4139 relative max_delta = 1.053659e-14 Converged to tolerance of 1.053659e-14 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4139 Final dimensionless free energies f_k = [ 0. 3.41393395] Computing normalized weights... Interval 4, DeltaF=3.4139 +/- 0.3011, Sum=9.0888 +/- 0.0881 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 773 N_k = [381 392] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.38325867] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.67880812] relative max_delta = 4.353947e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7658 relative max_delta = 1.136083e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.5290 relative max_delta = 4.991431e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.4579 relative max_delta = 4.878576e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.4572 relative max_delta = 4.828682e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.4572 relative max_delta = 4.692005e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.4572 relative max_delta = 1.980945e-15 Converged to tolerance of 1.980945e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.4572 Final dimensionless free energies f_k = [ 0. 1.45717335] Computing normalized weights... Interval 5, DeltaF=1.4572 +/- 0.3249, Sum=9.9519 +/- 0.1081 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 818 N_k = [392 426] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.38270014] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.51593384] relative max_delta = 2.582380e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5237 relative max_delta = 1.477264e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5933 relative max_delta = 1.174004e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5935 relative max_delta = 2.567314e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5935 relative max_delta = 1.383151e-09 Converged to tolerance of 1.383151e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5935 Final dimensionless free energies f_k = [ 0. -0.59347896] Computing normalized weights... Interval 6, DeltaF=-0.5935 +/- 0.2327, Sum=9.6004 +/- 0.1127 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 619 N_k = [426 193] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00924248] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.39829027] relative max_delta = 2.782311e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4264 relative max_delta = 1.969888e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6811 relative max_delta = 1.515291e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6898 relative max_delta = 5.150002e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6898 relative max_delta = 6.122529e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6898 relative max_delta = 8.656216e-12 Converged to tolerance of 8.656216e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6898 Final dimensionless free energies f_k = [ 0. -1.68984143] Computing normalized weights... Interval 7, DeltaF=-1.6898 +/- 0.2779, Sum=8.5994 +/- 0.1216 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 439 N_k = [193 246] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.69344387] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.1560098] relative max_delta = 2.145472e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1789 relative max_delta = 1.050092e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3843 relative max_delta = 8.613313e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3821 relative max_delta = 8.843675e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3821 relative max_delta = 7.593302e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3821 relative max_delta = 3.728479e-16 Converged to tolerance of 3.728479e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3821 Final dimensionless free energies f_k = [ 0. -2.38214649] Computing normalized weights... Interval 8, DeltaF=-2.3821 +/- 0.2604, Sum=7.1884 +/- 0.1281 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 651 N_k = [246 405] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.28118871] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.74331892] relative max_delta = 1.684566e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7580 relative max_delta = 5.323035e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8897 relative max_delta = 4.555991e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8878 relative max_delta = 6.521742e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8878 relative max_delta = 1.238944e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8878 relative max_delta = 3.844571e-15 Converged to tolerance of 3.844571e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8878 Final dimensionless free energies f_k = [ 0. -2.88776846] Computing normalized weights... Interval 9, DeltaF=-2.8878 +/- 0.2121, Sum=5.4778 +/- 0.1308 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 825 N_k = [405 420] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.95229206] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.03420767] relative max_delta = 7.920616e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0350 relative max_delta = 7.442982e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0419 relative max_delta = 6.653951e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0419 relative max_delta = 6.570001e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0419 relative max_delta = 8.311407e-15 Converged to tolerance of 8.311407e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0419 Final dimensionless free energies f_k = [ 0. -1.04191014] Computing normalized weights... Interval 10, DeltaF=-1.0419 +/- 0.1460, Sum=4.8607 +/- 0.1315 Pairwise MBAR free energy: 4.8607 +/- 0.1315 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4255 N_k = [500 480 500 312 381 392 426 193 246 405 420] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.1489902 2.16623533 1.72213178 1.47164781 1.70759692 1.63131279 1.57890651 1.51719938 0.92452252 0.46451384] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.16829883 3.6061857 3.18874069 2.75154817 3.07594928 2.96289998 2.80436743 2.54765679 1.49335792 0.85582947] relative max_delta = 4.066926e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.4310 4.0158 4.1716 4.3154 4.7784 4.6209 4.3556 3.9380 2.6687 1.9842 relative max_delta = 3.562872e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.9311 7.8614 12.4720 17.5159 19.1737 18.6133 17.3311 15.3545 12.1617 11.0679 relative max_delta = 7.507817e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8003 8.8704 12.1543 16.1138 17.5954 17.0098 15.3386 13.0351 10.1113 9.0612 relative max_delta = 1.318135e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7989 8.7857 11.9761 15.4286 16.9027 16.3124 14.6257 12.2929 9.3953 8.3439 relative max_delta = 4.391431e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7983 8.7860 11.9648 15.3761 16.8516 16.2613 14.5745 12.2415 9.3442 8.2927 relative max_delta = 3.114426e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7983 8.7860 11.9647 15.3758 16.8513 16.2610 14.5742 12.2412 9.3439 8.2924 relative max_delta = 1.902333e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7983 8.7860 11.9647 15.3758 16.8513 16.2610 14.5742 12.2412 9.3439 8.2924 relative max_delta = 7.011969e-10 Converged to tolerance of 7.011969e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7983 8.7860 11.9647 15.3758 16.8513 16.2610 14.5742 12.2412 9.3439 8.2924 Final dimensionless free energies f_k = [ 0. 6.79830641 8.78595097 11.96468987 15.37581247 16.85132868 16.26096905 14.57420028 12.24120436 9.34386493 8.29242303] Computing normalized weights... DeltaMij: [[ 0. 4.02689077 5.20424687 7.08713263 9.10766794 9.98167129 9.63197923 8.6328431 7.25092249 5.53472014 4.91191184] [-4.02689077 0. 1.1773561 3.06024186 5.08077717 5.95478052 5.60508847 4.60595233 3.22403172 1.50782938 0.88502107] [-5.20424687 -1.1773561 0. 1.88288576 3.90342107 4.77742442 4.42773237 3.42859623 2.04667562 0.33047328 -0.29233503] [-7.08713263 -3.06024186 -1.88288576 0. 2.02053531 2.89453866 2.5448466 1.54571047 0.16378986 -1.55241249 -2.17522079] [-9.10766794 -5.08077717 -3.90342107 -2.02053531 0. 0.87400335 0.5243113 -0.47482484 -1.85674545 -3.57294779 -4.1957561 ] [-9.98167129 -5.95478052 -4.77742442 -2.89453866 -0.87400335 0. -0.34969205 -1.34882819 -2.7307488 -4.44695114 -5.06975945] [-9.63197923 -5.60508847 -4.42773237 -2.5448466 -0.5243113 0.34969205 0. -0.99913614 -2.38105674 -4.09725909 -4.72006739] [-8.6328431 -4.60595233 -3.42859623 -1.54571047 0.47482484 1.34882819 0.99913614 0. -1.38192061 -3.09812295 -3.72093126] [-7.25092249 -3.22403172 -2.04667562 -0.16378986 1.85674545 2.7307488 2.38105674 1.38192061 0. -1.71620235 -2.33901065] [-5.53472014 -1.50782938 -0.33047328 1.55241249 3.57294779 4.44695114 4.09725909 3.09812295 1.71620235 0. -0.6228083 ] [-4.91191184 -0.88502107 0.29233503 2.17522079 4.1957561 5.06975945 4.72006739 3.72093126 2.33901065 0.6228083 0. ]] dDeltaMij: [[ 0. 0.04946768 0.0618184 0.07713237 0.09715251 0.11997504 0.12870559 0.1394772 0.14997253 0.15580108 0.15767102] [ 0.04946768 0. 0.0213937 0.05003999 0.07745793 0.10466746 0.11457047 0.12655099 0.13803269 0.14434417 0.14636056] [ 0.0618184 0.0213937 0. 0.03871382 0.07100431 0.09998884 0.11031263 0.12270956 0.13451954 0.14098838 0.14305207] [ 0.07713237 0.05003999 0.03871382 0. 0.05119462 0.08696918 0.0986658 0.11235519 0.12514616 0.13207489 0.13427565] [ 0.09715251 0.07745793 0.07100431 0.05119462 0. 0.05944025 0.07547195 0.09265694 0.10781058 0.11578144 0.11828574] [ 0.11997504 0.10466746 0.09998884 0.08696918 0.05944025 0. 0.03109061 0.06171917 0.08277996 0.09292104 0.09602325] [ 0.12870559 0.11457047 0.11031263 0.0986658 0.07547195 0.03109061 0. 0.04212 0.06883948 0.08079501 0.08434591] [ 0.1394772 0.12655099 0.12270956 0.11235519 0.09265694 0.06171917 0.04212 0. 0.03489192 0.05261471 0.05794955] [ 0.14997253 0.13803269 0.13451954 0.12514616 0.10781058 0.08277996 0.06883948 0.03489192 0. 0.02270337 0.03122146] [ 0.15580108 0.14434417 0.14098838 0.13207489 0.11578144 0.09292104 0.08079501 0.05261471 0.02270337 0. 0.01102475] [ 0.15767102 0.14636056 0.14305207 0.13427565 0.11828574 0.09602325 0.08434591 0.05794955 0.03122146 0.01102475 0. ]] Replica 16 / 40 Computing statistical inefficiencies: lambda 0: g = 1.108 lambda 1: g = 1.862 lambda 2: g = 1.708 lambda 3: g = 2.467 lambda 4: g = 1.689 lambda 5: g = 1.859 lambda 6: g = 1.000 lambda 7: g = 2.804 lambda 8: g = 2.364 lambda 9: g = 1.841 lambda 10: g = 2.363 Subsampling data to produce uncorrelated samples... number of samples per lambda: [380 394 294 500 332 405 497 200 349 358 273] Method: EXP Forward EXP: Interval 1, DeltaF=6.9963 +/- 0.4115, Sum=4.1441 +/- 0.1003 Interval 2, DeltaF=1.8051 +/- 0.3272, Sum=5.2134 +/- 0.1187 Interval 3, DeltaF=3.6728 +/- 0.3441, Sum=7.3889 +/- 0.1379 Interval 4, DeltaF=3.7041 +/- 0.5057, Sum=9.5830 +/- 0.2048 Interval 5, DeltaF=1.9062 +/- 0.4292, Sum=10.7121 +/- 0.2321 Interval 6, DeltaF=-0.2564 +/- 0.2836, Sum=10.5603 +/- 0.2369 Interval 7, DeltaF=-2.1710 +/- 0.6129, Sum=9.2743 +/- 0.3250 Interval 8, DeltaF=-2.3241 +/- 0.3453, Sum=7.8977 +/- 0.3326 Interval 9, DeltaF=-2.8572 +/- 0.2711, Sum=6.2053 +/- 0.3354 Interval 10, DeltaF=-1.1305 +/- 0.1708, Sum=5.5357 +/- 0.3359 Forward EXP free energy: 5.5357 +/- 0.3359 Reverse EXP: Interval 1, DeltaF=6.9704 +/- 0.5484, Sum=4.1288 +/- 0.1781 Interval 2, DeltaF=2.2783 +/- 0.4146, Sum=5.4783 +/- 0.2052 Interval 3, DeltaF=3.1892 +/- 0.3674, Sum=7.3674 +/- 0.2202 Interval 4, DeltaF=3.0346 +/- 0.4068, Sum=9.1649 +/- 0.2410 Interval 5, DeltaF=1.1565 +/- 0.4951, Sum=9.8499 +/- 0.2814 Interval 6, DeltaF=-0.7162 +/- 0.2704, Sum=9.4257 +/- 0.2847 Interval 7, DeltaF=-1.6605 +/- 0.4014, Sum=8.4421 +/- 0.3003 Interval 8, DeltaF=-2.4144 +/- 0.2914, Sum=7.0120 +/- 0.3044 Interval 9, DeltaF=-2.9559 +/- 0.3421, Sum=5.2611 +/- 0.3122 Interval 10, DeltaF=-1.0900 +/- 0.2072, Sum=4.6155 +/- 0.3133 Reverse EXP free energy: 4.6155 +/- 0.3133 Averge of forward and reverse EXP: Interval 1, DeltaF=6.9833 +/- 0.1878, Sum=4.1365 +/- 0.0209 Interval 2, DeltaF=2.0417 +/- 0.1102, Sum=5.3459 +/- 0.0221 Interval 3, DeltaF=3.4310 +/- 0.0977, Sum=7.3782 +/- 0.0228 Interval 4, DeltaF=3.3693 +/- 0.1658, Sum=9.3740 +/- 0.0280 Interval 5, DeltaF=1.5313 +/- 0.1669, Sum=10.2810 +/- 0.0325 Interval 6, DeltaF=-0.4863 +/- 0.0592, Sum=9.9930 +/- 0.0326 Interval 7, DeltaF=-1.9157 +/- 0.2224, Sum=8.8582 +/- 0.0438 Interval 8, DeltaF=-2.3692 +/- 0.0797, Sum=7.4548 +/- 0.0440 Interval 9, DeltaF=-2.9065 +/- 0.0752, Sum=5.7332 +/- 0.0441 Interval 10, DeltaF=-1.1102 +/- 0.0282, Sum=5.0756 +/- 0.0441 Average EXP free energy: 5.0756 +/- 0.0441 Interval 1, DeltaF=6.9704 +/- 0.2314, Sum=4.1288 +/- 0.0317 Interval 2, DeltaF=1.8051 +/- 0.2019, Sum=5.1981 +/- 0.0399 Interval 3, DeltaF=3.1892 +/- 0.3910, Sum=7.0872 +/- 0.0990 Interval 4, DeltaF=3.7041 +/- 0.3208, Sum=9.2812 +/- 0.1162 Interval 5, DeltaF=1.1565 +/- 0.4814, Sum=9.9663 +/- 0.1799 Interval 6, DeltaF=-0.2564 +/- 0.4309, Sum=9.8144 +/- 0.2108 Interval 7, DeltaF=-1.6605 +/- 0.5376, Sum=8.8309 +/- 0.2716 Interval 8, DeltaF=-2.3241 +/- 0.6042, Sum=7.4542 +/- 0.3472 Interval 9, DeltaF=-2.9559 +/- 0.5666, Sum=5.7033 +/- 0.3958 Interval 10, DeltaF=-1.1305 +/- 0.6168, Sum=5.0337 +/- 0.4555 Double-Wide EXP free energy: 5.0337 +/- 0.4555 Method: BAR Interval 1, DeltaF=6.7486 +/- 0.3170, Sum=3.9975 +/- 0.0595 Interval 2, DeltaF=1.9342 +/- 0.2138, Sum=5.1432 +/- 0.0654 Interval 3, DeltaF=3.1845 +/- 0.2640, Sum=7.0295 +/- 0.0773 Interval 4, DeltaF=3.2716 +/- 0.3009, Sum=8.9673 +/- 0.0941 Interval 5, DeltaF=0.9391 +/- 0.3354, Sum=9.5236 +/- 0.1153 Interval 6, DeltaF=-0.6282 +/- 0.2225, Sum=9.1515 +/- 0.1190 Interval 7, DeltaF=-1.7341 +/- 0.2730, Sum=8.1243 +/- 0.1269 Interval 8, DeltaF=-2.3418 +/- 0.2414, Sum=6.7372 +/- 0.1315 Interval 9, DeltaF=-2.9643 +/- 0.2071, Sum=4.9814 +/- 0.1340 Interval 10, DeltaF=-1.1234 +/- 0.1498, Sum=4.3159 +/- 0.1346 BAR free energy: 4.3159 +/- 0.1346 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9447 +/- 0.4739, Sum=4.1136 +/- 0.1330 Interval 2, DeltaF=1.8816 +/- 0.3028, Sum=5.2281 +/- 0.1437 Interval 3, DeltaF=3.3655 +/- 0.2963, Sum=7.2216 +/- 0.1528 Interval 4, DeltaF=3.2409 +/- 0.4289, Sum=9.1413 +/- 0.1877 Interval 5, DeltaF=0.9337 +/- 0.3575, Sum=9.6944 +/- 0.2024 Interval 6, DeltaF=-0.6490 +/- 0.2245, Sum=9.3100 +/- 0.2046 Interval 7, DeltaF=-1.7164 +/- 0.2075, Sum=8.2933 +/- 0.2062 Interval 8, DeltaF=-2.3771 +/- 0.3715, Sum=6.8852 +/- 0.2218 Interval 9, DeltaF=-2.9952 +/- 0.3495, Sum=5.1110 +/- 0.2333 Interval 10, DeltaF=-1.1123 +/- 0.1955, Sum=4.4522 +/- 0.2344 Unopt. BAR free energy: 4.4522 +/- 0.2344 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7569 +/- 0.3181, Sum=4.0023 +/- 0.0600 Interval 2, DeltaF=1.9367 +/- 0.2130, Sum=5.1495 +/- 0.0657 Interval 3, DeltaF=3.1868 +/- 0.2618, Sum=7.0372 +/- 0.0772 Interval 4, DeltaF=3.2855 +/- 0.3122, Sum=8.9833 +/- 0.0964 Interval 5, DeltaF=0.9399 +/- 0.3340, Sum=9.5400 +/- 0.1169 Interval 6, DeltaF=-0.6145 +/- 0.2270, Sum=9.1761 +/- 0.1208 Interval 7, DeltaF=-1.7387 +/- 0.2853, Sum=8.1462 +/- 0.1301 Interval 8, DeltaF=-2.3451 +/- 0.2539, Sum=6.7571 +/- 0.1356 Interval 9, DeltaF=-2.9628 +/- 0.2067, Sum=5.0021 +/- 0.1379 Interval 10, DeltaF=-1.1224 +/- 0.1441, Sum=4.3373 +/- 0.1384 Postopt. BAR free energy: 4.3373 +/- 0.1384 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 774 N_k = [380 394] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.46588344] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.75858724] relative max_delta = 2.716571e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9536 relative max_delta = 3.936112e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7080 relative max_delta = 2.615486e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7486 relative max_delta = 6.007373e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7486 relative max_delta = 4.843225e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7486 relative max_delta = 3.119131e-12 Converged to tolerance of 3.119131e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7486 Final dimensionless free energies f_k = [ 0. 6.7486188] Computing normalized weights... Interval 1, DeltaF=6.7486 +/- 0.3170, Sum=3.9975 +/- 0.0595 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 688 N_k = [394 294] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.51281852] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82740461] relative max_delta = 1.721491e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8381 relative max_delta = 5.836155e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9346 relative max_delta = 4.985437e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9342 relative max_delta = 2.005536e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9342 relative max_delta = 2.668092e-09 Converged to tolerance of 2.668092e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9342 Final dimensionless free energies f_k = [ 0. 1.93419157] Computing normalized weights... Interval 2, DeltaF=1.9342 +/- 0.2138, Sum=5.1432 +/- 0.0654 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 794 N_k = [294 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.62609779] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.4279799] relative max_delta = 3.302672e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5025 relative max_delta = 2.978325e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1741 relative max_delta = 2.115916e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1845 relative max_delta = 3.253987e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1845 relative max_delta = 1.582177e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1845 relative max_delta = 3.795920e-13 Converged to tolerance of 3.795920e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1845 Final dimensionless free energies f_k = [ 0. 3.18450016] Computing normalized weights... Interval 3, DeltaF=3.1845 +/- 0.2640, Sum=7.0295 +/- 0.0773 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 832 N_k = [500 332] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.84221228] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.52362523] relative max_delta = 4.472313e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7678 relative max_delta = 1.381205e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7730 relative max_delta = 5.314618e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3082 relative max_delta = 1.405086e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2718 relative max_delta = 1.111379e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2716 relative max_delta = 6.821888e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.2716 relative max_delta = 2.563317e-09 Converged to tolerance of 2.563317e-09 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2716 Final dimensionless free energies f_k = [ 0. 3.27158631] Computing normalized weights... Interval 4, DeltaF=3.2716 +/- 0.3009, Sum=8.9673 +/- 0.0941 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 737 N_k = [332 405] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.25704612] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.44854151] relative max_delta = 4.269290e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5001 relative max_delta = 1.030408e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 0.9588 relative max_delta = 4.784597e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 0.9391 relative max_delta = 2.101454e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 0.9391 relative max_delta = 4.093840e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 0.9391 relative max_delta = 1.551458e-10 Converged to tolerance of 1.551458e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 0.9391 Final dimensionless free energies f_k = [ 0. 0.93905787] Computing normalized weights... Interval 5, DeltaF=0.9391 +/- 0.3354, Sum=9.5236 +/- 0.1153 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 902 N_k = [405 497] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.42095441] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.5564543] relative max_delta = 2.435059e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5636 relative max_delta = 1.270759e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.6281 relative max_delta = 1.026520e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.6282 relative max_delta = 1.180912e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.6282 relative max_delta = 1.924582e-10 Converged to tolerance of 1.924582e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.6282 Final dimensionless free energies f_k = [ 0. -0.62816553] Computing normalized weights... Interval 6, DeltaF=-0.6282 +/- 0.2225, Sum=9.1515 +/- 0.1190 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 697 N_k = [497 200] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.03769847] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.43565907] relative max_delta = 2.771972e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4643 relative max_delta = 1.954812e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7240 relative max_delta = 1.506692e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7341 relative max_delta = 5.787513e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7341 relative max_delta = 8.634976e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7341 relative max_delta = 1.921427e-11 Converged to tolerance of 1.921427e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7341 Final dimensionless free energies f_k = [ 0. -1.73409426] Computing normalized weights... Interval 7, DeltaF=-1.7341 +/- 0.2730, Sum=8.1243 +/- 0.1269 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 549 N_k = [200 349] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.76338583] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.1719895] relative max_delta = 1.881242e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1892 relative max_delta = 7.875841e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3439 relative max_delta = 6.597759e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3418 relative max_delta = 8.992626e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3418 relative max_delta = 1.529037e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3418 relative max_delta = 3.603129e-15 Converged to tolerance of 3.603129e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3418 Final dimensionless free energies f_k = [ 0. -2.34176852] Computing normalized weights... Interval 8, DeltaF=-2.3418 +/- 0.2414, Sum=6.7372 +/- 0.1315 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 707 N_k = [349 358] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.26009973] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.78606052] relative max_delta = 1.887830e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8040 relative max_delta = 6.399673e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9652 relative max_delta = 5.437227e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9643 relative max_delta = 3.290408e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9643 relative max_delta = 8.035960e-09 Converged to tolerance of 8.035960e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9643 Final dimensionless free energies f_k = [ 0. -2.96425621] Computing normalized weights... Interval 9, DeltaF=-2.9643 +/- 0.2071, Sum=4.9814 +/- 0.1340 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 631 N_k = [358 273] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.0378584] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.11716554] relative max_delta = 7.098960e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.1178 relative max_delta = 5.575828e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.1234 relative max_delta = 4.993538e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.1234 relative max_delta = 1.513798e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.1234 relative max_delta = 1.401367e-13 Converged to tolerance of 1.401367e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.1234 Final dimensionless free energies f_k = [ 0. -1.12340023] Computing normalized weights... Interval 10, DeltaF=-1.1234 +/- 0.1498, Sum=4.3159 +/- 0.1346 Pairwise MBAR free energy: 4.3159 +/- 0.1346 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3982 N_k = [380 394 294 500 332 405 497 200 349 358 273] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.91638499 1.87675546 1.91509033 1.57142294 1.66711213 1.64436312 1.60456768 1.48973575 0.77818355 0.30506064] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.86559138 3.17173584 3.46008685 2.94084454 3.04062558 2.97815458 2.82974079 2.48854854 1.26023512 0.58835112] relative max_delta = 4.465196e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1382 3.5805 4.2580 4.4263 4.6120 4.4969 4.2392 3.7346 2.3101 1.5932 relative max_delta = 3.407114e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7419 7.4381 11.2575 16.9291 17.8778 17.2852 15.9849 13.9191 10.7512 9.6379 relative max_delta = 7.420276e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7648 8.8012 11.9996 15.8839 16.7548 16.1309 14.4321 12.0817 9.1077 8.0078 relative max_delta = 1.096625e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8008 8.7333 11.8735 15.2152 16.0960 15.4675 13.7521 11.3871 8.4240 7.3237 relative max_delta = 4.315770e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7997 8.7338 11.8675 15.1492 16.0317 15.4031 13.6877 11.3226 8.3596 7.2593 relative max_delta = 4.120882e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7997 8.7338 11.8675 15.1485 16.0310 15.4024 13.6870 11.3219 8.3589 7.2586 relative max_delta = 4.510746e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7997 8.7338 11.8675 15.1485 16.0310 15.4024 13.6870 11.3219 8.3589 7.2586 relative max_delta = 5.376317e-09 Converged to tolerance of 5.376317e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7997 8.7338 11.8675 15.1485 16.0310 15.4024 13.6870 11.3219 8.3589 7.2586 Final dimensionless free energies f_k = [ 0. 6.79974289 8.73375026 11.86747815 15.14845934 16.03102609 15.40241205 13.68702217 11.32194404 8.35892684 7.25857302] Computing normalized weights... DeltaMij: [[ 0. 4.02774165 5.17332644 7.0295505 8.97299818 9.49577543 9.12342386 8.10733437 6.70641027 4.95130453 4.29952387] [-4.02774165 0. 1.14558479 3.00180885 4.94525654 5.46803378 5.09568221 4.07959272 2.67866862 0.92356288 0.27178222] [-5.17332644 -1.14558479 0. 1.85622406 3.79967175 4.32244899 3.95009742 2.93400793 1.53308383 -0.22202191 -0.87380257] [-7.0295505 -3.00180885 -1.85622406 0. 1.94344769 2.46622494 2.09387337 1.07778388 -0.32314022 -2.07824597 -2.73002662] [-8.97299818 -4.94525654 -3.79967175 -1.94344769 0. 0.52277725 0.15042568 -0.86566381 -2.26658791 -4.02169365 -4.67347431] [-9.49577543 -5.46803378 -4.32244899 -2.46622494 -0.52277725 0. -0.37235157 -1.38844106 -2.78936516 -4.5444709 -5.19625156] [-9.12342386 -5.09568221 -3.95009742 -2.09387337 -0.15042568 0.37235157 0. -1.01608949 -2.41701359 -4.17211933 -4.82389999] [-8.10733437 -4.07959272 -2.93400793 -1.07778388 0.86566381 1.38844106 1.01608949 0. -1.4009241 -3.15602984 -3.8078105 ] [-6.70641027 -2.67866862 -1.53308383 0.32314022 2.26658791 2.78936516 2.41701359 1.4009241 0. -1.75510574 -2.4068864 ] [-4.95130453 -0.92356288 0.22202191 2.07824597 4.02169365 4.5444709 4.17211933 3.15602984 1.75510574 0. -0.65178066] [-4.29952387 -0.27178222 0.87380257 2.73002662 4.67347431 5.19625156 4.82389999 3.8078105 2.4068864 0.65178066 0. ]] dDeltaMij: [[ 0. 0.0580408 0.07200285 0.08569973 0.10410905 0.12995184 0.13718488 0.1463126 0.15506925 0.16010917 0.16202064] [ 0.0580408 0. 0.02492283 0.05159944 0.07849953 0.1105036 0.11892542 0.12934813 0.13917627 0.14477054 0.14688176] [ 0.07200285 0.02492283 0. 0.03636471 0.06972799 0.10445591 0.11332803 0.12422128 0.13442478 0.14020876 0.14238764] [ 0.08569973 0.05159944 0.03636471 0. 0.05280619 0.09396984 0.10374322 0.11554365 0.12644932 0.1325817 0.13488383] [ 0.10410905 0.07849953 0.06972799 0.05280619 0. 0.06551352 0.07884744 0.09383502 0.10697691 0.11416014 0.11682585] [ 0.12995184 0.1105036 0.10445591 0.09396984 0.06551352 0. 0.0286872 0.05803305 0.07754021 0.08718156 0.09064408] [ 0.13718488 0.11892542 0.11332803 0.10374322 0.07884744 0.0286872 0. 0.03995759 0.06457833 0.07591793 0.07987067] [ 0.1463126 0.12934813 0.12422128 0.11554365 0.09383502 0.05803305 0.03995759 0. 0.0323519 0.04950866 0.05545091] [ 0.15506925 0.13917627 0.13442478 0.12644932 0.10697691 0.07754021 0.06457833 0.0323519 0. 0.0224312 0.03178178] [ 0.16010917 0.14477054 0.14020876 0.1325817 0.11416014 0.08718156 0.07591793 0.04950866 0.0224312 0. 0.01193986] [ 0.16202064 0.14688176 0.14238764 0.13488383 0.11682585 0.09064408 0.07987067 0.05545091 0.03178178 0.01193986 0. ]] Replica 17 / 40 Computing statistical inefficiencies: lambda 0: g = 1.000 lambda 1: g = 2.236 lambda 2: g = 1.363 lambda 3: g = 1.639 lambda 4: g = 1.615 lambda 5: g = 1.379 lambda 6: g = 1.527 lambda 7: g = 2.156 lambda 8: g = 1.886 lambda 9: g = 2.073 lambda 10: g = 1.658 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 500 500 377 424 348 220 212 294 326] Method: EXP Forward EXP: Interval 1, DeltaF=6.8226 +/- 0.4300, Sum=4.0413 +/- 0.1095 Interval 2, DeltaF=1.9674 +/- 0.2659, Sum=5.2066 +/- 0.1172 Interval 3, DeltaF=3.2574 +/- 0.3538, Sum=7.1361 +/- 0.1387 Interval 4, DeltaF=3.8886 +/- 0.3845, Sum=9.4394 +/- 0.1640 Interval 5, DeltaF=2.1975 +/- 0.4286, Sum=10.7411 +/- 0.1969 Interval 6, DeltaF=-0.3686 +/- 0.3082, Sum=10.5228 +/- 0.2047 Interval 7, DeltaF=-1.3852 +/- 0.3944, Sum=9.7022 +/- 0.2245 Interval 8, DeltaF=-2.5026 +/- 0.4471, Sum=8.2198 +/- 0.2538 Interval 9, DeltaF=-2.8575 +/- 0.2840, Sum=6.5272 +/- 0.2583 Interval 10, DeltaF=-1.0419 +/- 0.1750, Sum=5.9101 +/- 0.2589 Forward EXP free energy: 5.9101 +/- 0.2589 Reverse EXP: Interval 1, DeltaF=6.7762 +/- 0.4383, Sum=4.0138 +/- 0.1138 Interval 2, DeltaF=1.9486 +/- 0.2727, Sum=5.1680 +/- 0.1220 Interval 3, DeltaF=3.1061 +/- 0.3579, Sum=7.0079 +/- 0.1437 Interval 4, DeltaF=3.4105 +/- 0.4104, Sum=9.0280 +/- 0.1749 Interval 5, DeltaF=1.3066 +/- 0.4485, Sum=9.8019 +/- 0.2117 Interval 6, DeltaF=-0.5248 +/- 0.3076, Sum=9.4911 +/- 0.2190 Interval 7, DeltaF=-1.4806 +/- 0.3970, Sum=8.6141 +/- 0.2380 Interval 8, DeltaF=-2.2909 +/- 0.3886, Sum=7.2571 +/- 0.2543 Interval 9, DeltaF=-2.9132 +/- 0.3495, Sum=5.5315 +/- 0.2644 Interval 10, DeltaF=-1.0575 +/- 0.1873, Sum=4.9051 +/- 0.2652 Reverse EXP free energy: 4.9051 +/- 0.2652 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7994 +/- 0.1451, Sum=4.0275 +/- 0.0125 Interval 2, DeltaF=1.9580 +/- 0.0559, Sum=5.1873 +/- 0.0126 Interval 3, DeltaF=3.1818 +/- 0.0975, Sum=7.0720 +/- 0.0138 Interval 4, DeltaF=3.6495 +/- 0.1220, Sum=9.2337 +/- 0.0164 Interval 5, DeltaF=1.7520 +/- 0.1483, Sum=10.2715 +/- 0.0209 Interval 6, DeltaF=-0.4467 +/- 0.0729, Sum=10.0069 +/- 0.0212 Interval 7, DeltaF=-1.4329 +/- 0.1205, Sum=9.1581 +/- 0.0228 Interval 8, DeltaF=-2.3968 +/- 0.1363, Sum=7.7385 +/- 0.0254 Interval 9, DeltaF=-2.8853 +/- 0.0796, Sum=6.0294 +/- 0.0256 Interval 10, DeltaF=-1.0497 +/- 0.0253, Sum=5.4076 +/- 0.0256 Average EXP free energy: 5.4076 +/- 0.0256 Interval 1, DeltaF=6.7762 +/- 0.1478, Sum=4.0138 +/- 0.0129 Interval 2, DeltaF=1.9674 +/- 0.2085, Sum=5.1791 +/- 0.0288 Interval 3, DeltaF=3.1061 +/- 0.2449, Sum=7.0190 +/- 0.0457 Interval 4, DeltaF=3.8886 +/- 0.2791, Sum=9.3223 +/- 0.0650 Interval 5, DeltaF=1.3066 +/- 0.3568, Sum=10.0963 +/- 0.0995 Interval 6, DeltaF=-0.3686 +/- 0.3690, Sum=9.8779 +/- 0.1281 Interval 7, DeltaF=-1.4806 +/- 0.4202, Sum=9.0009 +/- 0.1654 Interval 8, DeltaF=-2.5026 +/- 0.4403, Sum=7.5185 +/- 0.2014 Interval 9, DeltaF=-2.9132 +/- 0.4766, Sum=5.7930 +/- 0.2422 Interval 10, DeltaF=-1.0419 +/- 0.4752, Sum=5.1758 +/- 0.2766 Double-Wide EXP free energy: 5.1758 +/- 0.2766 Method: BAR Interval 1, DeltaF=6.8301 +/- 0.2912, Sum=4.0457 +/- 0.0502 Interval 2, DeltaF=1.9776 +/- 0.1964, Sum=5.2172 +/- 0.0552 Interval 3, DeltaF=3.1927 +/- 0.2487, Sum=7.1083 +/- 0.0662 Interval 4, DeltaF=3.3795 +/- 0.2972, Sum=9.1102 +/- 0.0844 Interval 5, DeltaF=1.2743 +/- 0.3282, Sum=9.8650 +/- 0.1058 Interval 6, DeltaF=-0.5814 +/- 0.2371, Sum=9.5206 +/- 0.1109 Interval 7, DeltaF=-1.5415 +/- 0.2692, Sum=8.6075 +/- 0.1189 Interval 8, DeltaF=-2.2617 +/- 0.2628, Sum=7.2678 +/- 0.1258 Interval 9, DeltaF=-2.9226 +/- 0.2245, Sum=5.5367 +/- 0.1293 Interval 10, DeltaF=-1.0617 +/- 0.1511, Sum=4.9078 +/- 0.1300 BAR free energy: 4.9078 +/- 0.1300 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.7883 +/- 0.4626, Sum=4.0209 +/- 0.1267 Interval 2, DeltaF=1.9739 +/- 0.2566, Sum=5.1902 +/- 0.1326 Interval 3, DeltaF=3.1246 +/- 0.3189, Sum=7.0410 +/- 0.1456 Interval 4, DeltaF=3.3485 +/- 0.3897, Sum=9.0244 +/- 0.1712 Interval 5, DeltaF=1.2649 +/- 0.3632, Sum=9.7737 +/- 0.1882 Interval 6, DeltaF=-0.5802 +/- 0.2276, Sum=9.4300 +/- 0.1907 Interval 7, DeltaF=-1.5489 +/- 0.2462, Sum=8.5125 +/- 0.1940 Interval 8, DeltaF=-2.2864 +/- 0.3276, Sum=7.1582 +/- 0.2042 Interval 9, DeltaF=-2.9351 +/- 0.4108, Sum=5.4196 +/- 0.2273 Interval 10, DeltaF=-1.0595 +/- 0.2280, Sum=4.7921 +/- 0.2294 Unopt. BAR free energy: 4.7921 +/- 0.2294 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8352 +/- 0.2918, Sum=4.0488 +/- 0.0504 Interval 2, DeltaF=1.9776 +/- 0.1965, Sum=5.2202 +/- 0.0554 Interval 3, DeltaF=3.1886 +/- 0.2495, Sum=7.1089 +/- 0.0665 Interval 4, DeltaF=3.3716 +/- 0.3091, Sum=9.1061 +/- 0.0873 Interval 5, DeltaF=1.2713 +/- 0.3364, Sum=9.8591 +/- 0.1101 Interval 6, DeltaF=-0.5795 +/- 0.2484, Sum=9.5159 +/- 0.1160 Interval 7, DeltaF=-1.5367 +/- 0.2866, Sum=8.6056 +/- 0.1258 Interval 8, DeltaF=-2.2609 +/- 0.2631, Sum=7.2664 +/- 0.1323 Interval 9, DeltaF=-2.9209 +/- 0.2219, Sum=5.5362 +/- 0.1355 Interval 10, DeltaF=-1.0617 +/- 0.1530, Sum=4.9074 +/- 0.1362 Postopt. BAR free energy: 4.9074 +/- 0.1362 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.59938422] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.92109701] relative max_delta = 2.685809e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1119 relative max_delta = 3.732776e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8217 relative max_delta = 2.506401e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8301 relative max_delta = 1.229141e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8301 relative max_delta = 1.476924e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8301 relative max_delta = 2.080621e-15 Converged to tolerance of 2.080621e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8301 Final dimensionless free energies f_k = [ 0. 6.83010287] Computing normalized weights... Interval 1, DeltaF=6.8301 +/- 0.2912, Sum=4.0457 +/- 0.0502 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.5044006] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.85158716] relative max_delta = 1.875075e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8642 relative max_delta = 6.761230e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9776 relative max_delta = 5.735597e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9776 relative max_delta = 1.222630e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9776 relative max_delta = 3.128271e-12 Converged to tolerance of 3.128271e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9776 Final dimensionless free energies f_k = [ 0. 1.97764386] Computing normalized weights... Interval 2, DeltaF=1.9776 +/- 0.1964, Sum=5.2172 +/- 0.0552 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.61954249] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.41754352] relative max_delta = 3.300876e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4973 relative max_delta = 3.195102e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2097 relative max_delta = 2.219358e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1928 relative max_delta = 5.301776e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1927 relative max_delta = 1.130004e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1927 relative max_delta = 5.313357e-14 Converged to tolerance of 5.313357e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1927 Final dimensionless free energies f_k = [ 0. 3.19274746] Computing normalized weights... Interval 3, DeltaF=3.1927 +/- 0.2487, Sum=7.1083 +/- 0.0662 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 877 N_k = [500 377] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.97771517] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.71198745] relative max_delta = 4.289005e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9187 relative max_delta = 1.077350e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6863 relative max_delta = 4.795031e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3912 relative max_delta = 8.699917e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3795 relative max_delta = 3.461737e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3795 relative max_delta = 5.332900e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3795 relative max_delta = 1.264096e-11 Converged to tolerance of 1.264096e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3795 Final dimensionless free energies f_k = [ 0. 3.3795294] Computing normalized weights... Interval 4, DeltaF=3.3795 +/- 0.2972, Sum=9.1102 +/- 0.0844 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 801 N_k = [377 424] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.32994453] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.58322524] relative max_delta = 4.342760e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6585 relative max_delta = 1.143710e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3237 relative max_delta = 5.024921e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2746 relative max_delta = 3.849921e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2743 relative max_delta = 2.425454e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2743 relative max_delta = 9.547275e-09 Converged to tolerance of 9.547275e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2743 Final dimensionless free energies f_k = [ 0. 1.27430371] Computing normalized weights... Interval 5, DeltaF=1.2743 +/- 0.3282, Sum=9.8650 +/- 0.1058 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 772 N_k = [424 348] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.37250307] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.50396782] relative max_delta = 2.608594e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5117 relative max_delta = 1.505781e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5811 relative max_delta = 1.194634e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5814 relative max_delta = 5.877360e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5814 relative max_delta = 1.484759e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5814 relative max_delta = 7.637835e-16 Converged to tolerance of 7.637835e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5814 Final dimensionless free energies f_k = [ 0. -0.58143337] Computing normalized weights... Interval 6, DeltaF=-0.5814 +/- 0.2371, Sum=9.5206 +/- 0.1109 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 568 N_k = [348 220] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96856792] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.31236957] relative max_delta = 2.619701e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3348 relative max_delta = 1.678917e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5373 relative max_delta = 1.317649e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5415 relative max_delta = 2.674383e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5415 relative max_delta = 1.183627e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5415 relative max_delta = 2.317718e-13 Converged to tolerance of 2.317718e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5415 Final dimensionless free energies f_k = [ 0. -1.54147218] Computing normalized weights... Interval 7, DeltaF=-1.5415 +/- 0.2692, Sum=8.6075 +/- 0.1189 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 432 N_k = [220 212] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.578979] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.03218604] relative max_delta = 2.230145e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0552 relative max_delta = 1.117895e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2618 relative max_delta = 9.137591e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2617 relative max_delta = 6.513366e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2617 relative max_delta = 6.238461e-11 Converged to tolerance of 6.238461e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2617 Final dimensionless free energies f_k = [ 0. -2.26169077] Computing normalized weights... Interval 8, DeltaF=-2.2617 +/- 0.2628, Sum=7.2678 +/- 0.1258 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 506 N_k = [212 294] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.26667619] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.76252094] relative max_delta = 1.794900e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7788 relative max_delta = 5.843548e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9244 relative max_delta = 4.980949e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9226 relative max_delta = 6.335223e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9226 relative max_delta = 9.086980e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9226 relative max_delta = 1.215612e-15 Converged to tolerance of 1.215612e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9226 Final dimensionless free energies f_k = [ 0. -2.92257098] Computing normalized weights... Interval 9, DeltaF=-2.9226 +/- 0.2245, Sum=5.5367 +/- 0.1293 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 620 N_k = [294 326] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98466077] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.05592795] relative max_delta = 6.749246e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0565 relative max_delta = 5.441270e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0617 relative max_delta = 4.873119e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0617 relative max_delta = 6.717112e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0617 relative max_delta = 1.275787e-14 Converged to tolerance of 1.275787e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0617 Final dimensionless free energies f_k = [ 0. -1.06167578] Computing normalized weights... Interval 10, DeltaF=-1.0617 +/- 0.1511, Sum=4.9078 +/- 0.1300 Pairwise MBAR free energy: 4.9078 +/- 0.1300 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4201 N_k = [500 500 500 500 377 424 348 220 212 294 326] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.01073746 1.95993207 1.87446205 1.55483494 1.6715219 1.63176948 1.55300152 1.45737876 0.89438934 0.46887791] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.99764575 3.32509599 3.4117129 2.91434996 3.04061292 2.95248401 2.76159997 2.47696445 1.46123979 0.85293556] relative max_delta = 4.505804e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2721 3.7447 4.3152 4.4331 4.7002 4.5659 4.2723 3.8388 2.6060 1.9457 relative max_delta = 3.530929e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8792 7.6847 11.9760 17.0694 18.5551 18.0027 16.7443 14.8677 11.6737 10.5617 relative max_delta = 7.466879e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8031 8.8574 12.0467 15.9413 17.2489 16.6710 15.1335 12.9031 9.9504 8.8914 relative max_delta = 1.138924e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8287 8.7953 11.9992 15.4147 16.7167 16.1355 14.5892 12.3304 9.4021 8.3412 relative max_delta = 3.426082e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8280 8.7953 11.9932 15.3714 16.6748 16.0936 14.5474 12.2884 9.3603 8.2994 relative max_delta = 2.596092e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8280 8.7953 11.9932 15.3711 16.6746 16.0934 14.5471 12.2881 9.3600 8.2991 relative max_delta = 1.541045e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8280 8.7953 11.9932 15.3711 16.6746 16.0934 14.5471 12.2881 9.3600 8.2991 relative max_delta = 5.595256e-10 Converged to tolerance of 5.595256e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8280 8.7953 11.9932 15.3711 16.6746 16.0934 14.5471 12.2881 9.3600 8.2991 Final dimensionless free energies f_k = [ 0. 6.82804806 8.79531912 11.99319316 15.37110415 16.67459382 16.09340206 14.54710724 12.28812951 9.36002487 8.29912911] Computing normalized weights... DeltaMij: [[ 0. 4.04450786 5.20979598 7.10401619 9.10487902 9.87698463 9.53272305 8.61679488 7.27871801 5.54429228 4.9158841 ] [-4.04450786 0. 1.16528812 3.05950833 5.06037116 5.83247677 5.48821519 4.57228702 3.23421015 1.49978442 0.87137625] [-5.20979598 -1.16528812 0. 1.89422022 3.89508305 4.66718866 4.32292707 3.40699891 2.06892204 0.3344963 -0.29391187] [-7.10401619 -3.05950833 -1.89422022 0. 2.00086283 2.77296844 2.42870686 1.51277869 0.17470182 -1.55972391 -2.18813209] [-9.10487902 -5.06037116 -3.89508305 -2.00086283 0. 0.77210561 0.42784403 -0.48808414 -1.82616101 -3.56058674 -4.18899492] [-9.87698463 -5.83247677 -4.66718866 -2.77296844 -0.77210561 0. -0.34426158 -1.26018975 -2.59826662 -4.33269235 -4.96110053] [-9.53272305 -5.48821519 -4.32292707 -2.42870686 -0.42784403 0.34426158 0. -0.91592817 -2.25400504 -3.98843077 -4.61683894] [-8.61679488 -4.57228702 -3.40699891 -1.51277869 0.48808414 1.26018975 0.91592817 0. -1.33807687 -3.0725026 -3.70091078] [-7.27871801 -3.23421015 -2.06892204 -0.17470182 1.82616101 2.59826662 2.25400504 1.33807687 0. -1.73442573 -2.36283391] [-5.54429228 -1.49978442 -0.3344963 1.55972391 3.56058674 4.33269235 3.98843077 3.0725026 1.73442573 0. -0.62840817] [-4.9158841 -0.87137625 0.29391187 2.18813209 4.18899492 4.96110053 4.61683894 3.70091078 2.36283391 0.62840817 0. ]] dDeltaMij: [[ 0. 0.04916205 0.06154455 0.07451817 0.09393247 0.11806844 0.12699105 0.13764624 0.14902071 0.15589835 0.15817667] [ 0.04916205 0. 0.02163705 0.04638676 0.07364426 0.10266634 0.11281377 0.12468643 0.13714004 0.14458394 0.14703768] [ 0.06154455 0.02163705 0. 0.03365489 0.06655549 0.09770627 0.10831935 0.12063516 0.13346733 0.14110511 0.1436183 ] [ 0.07451817 0.04638676 0.03365489 0. 0.05077258 0.08765547 0.09934881 0.11264962 0.12629577 0.1343419 0.13697923] [ 0.09393247 0.07364426 0.06655549 0.05077258 0. 0.06065443 0.0765388 0.09315898 0.10926681 0.11847516 0.12145751] [ 0.11806844 0.10266634 0.09770627 0.08765547 0.06065443 0. 0.03226729 0.06169194 0.08408991 0.09574855 0.09941492] [ 0.12699105 0.11281377 0.10831935 0.09934881 0.0765388 0.03226729 0. 0.04011797 0.06919557 0.08303507 0.08723856] [ 0.13764624 0.12468643 0.12063516 0.11264962 0.09315898 0.06169194 0.04011797 0. 0.03806365 0.05773313 0.06367313] [ 0.14902071 0.13714004 0.13346733 0.12629577 0.10926681 0.08408991 0.06919557 0.03806365 0. 0.02518983 0.03461903] [ 0.15589835 0.14458394 0.14110511 0.1343419 0.11847516 0.09574855 0.08303507 0.05773313 0.02518983 0. 0.01217165] [ 0.15817667 0.14703768 0.1436183 0.13697923 0.12145751 0.09941492 0.08723856 0.06367313 0.03461903 0.01217165 0. ]] Replica 18 / 40 Computing statistical inefficiencies: lambda 0: g = 1.062 lambda 1: g = 1.612 lambda 2: g = 1.115 lambda 3: g = 1.150 lambda 4: g = 2.295 lambda 5: g = 1.031 lambda 6: g = 1.988 lambda 7: g = 1.441 lambda 8: g = 1.801 lambda 9: g = 2.102 lambda 10: g = 1.816 Subsampling data to produce uncorrelated samples... number of samples per lambda: [355 356 405 500 350 500 173 231 239 219 416] Method: EXP Forward EXP: Interval 1, DeltaF=7.4351 +/- 0.4108, Sum=4.4041 +/- 0.1000 Interval 2, DeltaF=1.8529 +/- 0.2784, Sum=5.5016 +/- 0.1100 Interval 3, DeltaF=3.4309 +/- 0.3494, Sum=7.5339 +/- 0.1317 Interval 4, DeltaF=3.8319 +/- 0.3909, Sum=9.8036 +/- 0.1598 Interval 5, DeltaF=2.2576 +/- 0.5486, Sum=11.1409 +/- 0.2394 Interval 6, DeltaF=-0.7830 +/- 0.4346, Sum=10.6771 +/- 0.2642 Interval 7, DeltaF=-1.4727 +/- 0.6290, Sum=9.8048 +/- 0.3532 Interval 8, DeltaF=-2.3454 +/- 0.3402, Sum=8.4156 +/- 0.3598 Interval 9, DeltaF=-2.7289 +/- 0.2750, Sum=6.7991 +/- 0.3626 Interval 10, DeltaF=-0.9877 +/- 0.1993, Sum=6.2141 +/- 0.3633 Forward EXP free energy: 6.2141 +/- 0.3633 Reverse EXP: Interval 1, DeltaF=7.1257 +/- 0.6481, Sum=4.2208 +/- 0.2488 Interval 2, DeltaF=1.9842 +/- 0.3464, Sum=5.3961 +/- 0.2587 Interval 3, DeltaF=3.1949 +/- 0.3554, Sum=7.2886 +/- 0.2693 Interval 4, DeltaF=3.3928 +/- 0.3753, Sum=9.2983 +/- 0.2820 Interval 5, DeltaF=1.2086 +/- 0.4121, Sum=10.0142 +/- 0.2994 Interval 6, DeltaF=-0.6311 +/- 0.3499, Sum=9.6404 +/- 0.3080 Interval 7, DeltaF=-1.8058 +/- 0.3811, Sum=8.5707 +/- 0.3198 Interval 8, DeltaF=-2.2116 +/- 0.3222, Sum=7.2607 +/- 0.3257 Interval 9, DeltaF=-2.7173 +/- 0.3575, Sum=5.6511 +/- 0.3343 Interval 10, DeltaF=-0.9897 +/- 0.1900, Sum=5.0649 +/- 0.3350 Reverse EXP free energy: 5.0649 +/- 0.3350 Averge of forward and reverse EXP: Interval 1, DeltaF=7.2804 +/- 0.2463, Sum=4.3125 +/- 0.0359 Interval 2, DeltaF=1.9185 +/- 0.0777, Sum=5.4489 +/- 0.0361 Interval 3, DeltaF=3.3129 +/- 0.0956, Sum=7.4112 +/- 0.0365 Interval 4, DeltaF=3.6123 +/- 0.1131, Sum=9.5510 +/- 0.0373 Interval 5, DeltaF=1.7331 +/- 0.1881, Sum=10.5776 +/- 0.0428 Interval 6, DeltaF=-0.7071 +/- 0.1225, Sum=10.1588 +/- 0.0437 Interval 7, DeltaF=-1.6392 +/- 0.2294, Sum=9.1878 +/- 0.0537 Interval 8, DeltaF=-2.2785 +/- 0.0846, Sum=7.8381 +/- 0.0538 Interval 9, DeltaF=-2.7231 +/- 0.0808, Sum=6.2251 +/- 0.0540 Interval 10, DeltaF=-0.9887 +/- 0.0292, Sum=5.6395 +/- 0.0540 Average EXP free energy: 5.6395 +/- 0.0540 Interval 1, DeltaF=7.1257 +/- 0.3232, Sum=4.2208 +/- 0.0619 Interval 2, DeltaF=1.8529 +/- 0.1932, Sum=5.3184 +/- 0.0657 Interval 3, DeltaF=3.1949 +/- 0.4853, Sum=7.2109 +/- 0.1542 Interval 4, DeltaF=3.8319 +/- 0.2690, Sum=9.4806 +/- 0.1600 Interval 5, DeltaF=1.2086 +/- 0.5343, Sum=10.1966 +/- 0.2328 Interval 6, DeltaF=-0.7830 +/- 0.4633, Sum=9.7328 +/- 0.2653 Interval 7, DeltaF=-1.8058 +/- 0.5769, Sum=8.6631 +/- 0.3305 Interval 8, DeltaF=-2.3454 +/- 0.6551, Sum=7.2739 +/- 0.4170 Interval 9, DeltaF=-2.7173 +/- 0.6064, Sum=5.6643 +/- 0.4705 Interval 10, DeltaF=-0.9877 +/- 0.6670, Sum=5.0793 +/- 0.5392 Double-Wide EXP free energy: 5.0793 +/- 0.5392 Method: BAR Interval 1, DeltaF=6.9052 +/- 0.3228, Sum=4.0902 +/- 0.0617 Interval 2, DeltaF=1.9009 +/- 0.2116, Sum=5.2162 +/- 0.0672 Interval 3, DeltaF=3.1967 +/- 0.2461, Sum=7.1097 +/- 0.0761 Interval 4, DeltaF=3.4708 +/- 0.2946, Sum=9.1656 +/- 0.0919 Interval 5, DeltaF=1.3019 +/- 0.3185, Sum=9.9368 +/- 0.1098 Interval 6, DeltaF=-0.5986 +/- 0.2556, Sum=9.5822 +/- 0.1164 Interval 7, DeltaF=-1.6427 +/- 0.2934, Sum=8.6092 +/- 0.1271 Interval 8, DeltaF=-2.2640 +/- 0.2490, Sum=7.2681 +/- 0.1323 Interval 9, DeltaF=-2.7864 +/- 0.2293, Sum=5.6176 +/- 0.1359 Interval 10, DeltaF=-1.0042 +/- 0.1584, Sum=5.0228 +/- 0.1367 BAR free energy: 5.0228 +/- 0.1367 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=7.3784 +/- 0.4847, Sum=4.3705 +/- 0.1391 Interval 2, DeltaF=1.8698 +/- 0.2581, Sum=5.4780 +/- 0.1446 Interval 3, DeltaF=3.2430 +/- 0.3150, Sum=7.3990 +/- 0.1561 Interval 4, DeltaF=3.3342 +/- 0.4051, Sum=9.3740 +/- 0.1839 Interval 5, DeltaF=1.3495 +/- 0.3442, Sum=10.1733 +/- 0.1968 Interval 6, DeltaF=-0.5841 +/- 0.2172, Sum=9.8273 +/- 0.1988 Interval 7, DeltaF=-1.7398 +/- 0.3230, Sum=8.7967 +/- 0.2082 Interval 8, DeltaF=-2.2176 +/- 0.3286, Sum=7.4832 +/- 0.2178 Interval 9, DeltaF=-2.7502 +/- 0.3646, Sum=5.8541 +/- 0.2316 Interval 10, DeltaF=-0.9977 +/- 0.2640, Sum=5.2632 +/- 0.2352 Unopt. BAR free energy: 5.2632 +/- 0.2352 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.9051 +/- 0.3230, Sum=4.0902 +/- 0.0618 Interval 2, DeltaF=1.9027 +/- 0.2131, Sum=5.2172 +/- 0.0674 Interval 3, DeltaF=3.1979 +/- 0.2461, Sum=7.1114 +/- 0.0764 Interval 4, DeltaF=3.4471 +/- 0.3114, Sum=9.1533 +/- 0.0956 Interval 5, DeltaF=1.3090 +/- 0.3247, Sum=9.9286 +/- 0.1142 Interval 6, DeltaF=-0.6111 +/- 0.2806, Sum=9.5667 +/- 0.1233 Interval 7, DeltaF=-1.6183 +/- 0.2965, Sum=8.6081 +/- 0.1338 Interval 8, DeltaF=-2.2581 +/- 0.2505, Sum=7.2705 +/- 0.1389 Interval 9, DeltaF=-2.7841 +/- 0.2299, Sum=5.6214 +/- 0.1424 Interval 10, DeltaF=-1.0042 +/- 0.1590, Sum=5.0266 +/- 0.1432 Postopt. BAR free energy: 5.0266 +/- 0.1432 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 711 N_k = [355 356] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.44629418] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.78867447] relative max_delta = 2.803240e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0022 relative max_delta = 4.267972e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.9101 relative max_delta = 2.761091e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.9052 relative max_delta = 7.046806e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.9052 relative max_delta = 3.813361e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.9052 relative max_delta = 5.144951e-16 Converged to tolerance of 5.144951e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.9052 Final dimensionless free energies f_k = [ 0. 6.90524356] Computing normalized weights... Interval 1, DeltaF=6.9052 +/- 0.3228, Sum=4.0902 +/- 0.0617 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 761 N_k = [356 405] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.4435571] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.77732975] relative max_delta = 1.877944e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7897 relative max_delta = 6.884758e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9006 relative max_delta = 5.837867e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9009 relative max_delta = 1.727505e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9009 relative max_delta = 1.962864e-09 Converged to tolerance of 1.962864e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9009 Final dimensionless free energies f_k = [ 0. 1.90093429] Computing normalized weights... Interval 2, DeltaF=1.9009 +/- 0.2116, Sum=5.2162 +/- 0.0672 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 905 N_k = [405 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.66337599] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.48092338] relative max_delta = 3.295335e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5538 relative max_delta = 2.855215e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2061 relative max_delta = 2.034441e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1967 relative max_delta = 2.948943e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1967 relative max_delta = 2.043027e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1967 relative max_delta = 4.167663e-16 Converged to tolerance of 4.167663e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1967 Final dimensionless free energies f_k = [ 0. 3.19667764] Computing normalized weights... Interval 3, DeltaF=3.1967 +/- 0.2461, Sum=7.1097 +/- 0.0761 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 850 N_k = [500 350] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.00273242] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.76655163] relative max_delta = 4.323787e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9887 relative max_delta = 1.116935e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8578 relative max_delta = 4.845053e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4907 relative max_delta = 1.051780e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4709 relative max_delta = 5.692337e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4708 relative max_delta = 1.636390e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4708 relative max_delta = 1.350285e-10 Converged to tolerance of 1.350285e-10 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4708 Final dimensionless free energies f_k = [ 0. 3.47084141] Computing normalized weights... Interval 4, DeltaF=3.4708 +/- 0.2946, Sum=9.1656 +/- 0.0919 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 850 N_k = [350 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.36578165] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.63772044] relative max_delta = 4.264232e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7082 relative max_delta = 9.945775e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3340 relative max_delta = 4.691328e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3020 relative max_delta = 2.456645e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3019 relative max_delta = 6.936975e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3019 relative max_delta = 5.518827e-10 Converged to tolerance of 5.518827e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3019 Final dimensionless free energies f_k = [ 0. 1.30187751] Computing normalized weights... Interval 5, DeltaF=1.3019 +/- 0.3185, Sum=9.9368 +/- 0.1098 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 673 N_k = [500 173] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.39138783] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.52573181] relative max_delta = 2.555371e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5329 relative max_delta = 1.350875e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5979 relative max_delta = 1.086499e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5986 relative max_delta = 1.228380e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5986 relative max_delta = 1.573760e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5986 relative max_delta = 4.636536e-15 Converged to tolerance of 4.636536e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5986 Final dimensionless free energies f_k = [ 0. -0.59862737] Computing normalized weights... Interval 6, DeltaF=-0.5986 +/- 0.2556, Sum=9.5822 +/- 0.1164 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 404 N_k = [173 231] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.05531209] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.40639521] relative max_delta = 2.496333e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4300 relative max_delta = 1.651066e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6425 relative max_delta = 1.293632e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6427 relative max_delta = 1.212341e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6427 relative max_delta = 3.413148e-10 Converged to tolerance of 3.413148e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6427 Final dimensionless free energies f_k = [ 0. -1.6426814] Computing normalized weights... Interval 7, DeltaF=-1.6427 +/- 0.2934, Sum=8.6092 +/- 0.1271 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 470 N_k = [231 239] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.65154164] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.07593684] relative max_delta = 2.044355e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0948 relative max_delta = 9.003513e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2644 relative max_delta = 7.490673e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2640 relative max_delta = 1.630978e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2640 relative max_delta = 2.019543e-10 Converged to tolerance of 2.019543e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2640 Final dimensionless free energies f_k = [ 0. -2.26404824] Computing normalized weights... Interval 8, DeltaF=-2.2640 +/- 0.2490, Sum=7.2681 +/- 0.1323 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 458 N_k = [239 219] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.09443578] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.61279117] relative max_delta = 1.983914e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.6302 relative max_delta = 6.624931e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.7869 relative max_delta = 5.621301e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.7864 relative max_delta = 1.866066e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.7864 relative max_delta = 7.855097e-10 Converged to tolerance of 7.855097e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.7864 Final dimensionless free energies f_k = [ 0. -2.78635482] Computing normalized weights... Interval 9, DeltaF=-2.7864 +/- 0.2293, Sum=5.6176 +/- 0.1359 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 635 N_k = [219 416] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9282166] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.99795979] relative max_delta = 6.988577e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.9986 relative max_delta = 6.293653e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0042 relative max_delta = 5.631353e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0042 relative max_delta = 4.405671e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0042 relative max_delta = 2.687559e-12 Converged to tolerance of 2.687559e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0042 Final dimensionless free energies f_k = [ 0. -1.00423909] Computing normalized weights... Interval 10, DeltaF=-1.0042 +/- 0.1584, Sum=5.0228 +/- 0.1367 Pairwise MBAR free energy: 5.0228 +/- 0.1367 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3744 N_k = [355 356 405 500 350 500 173 231 239 219 416] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.87039811 1.87972079 1.95171877 1.607786 1.72650792 1.73576537 1.73824574 1.63279419 0.99640055 0.62974916] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.79885278 3.14143994 3.49065942 3.00012442 3.15413556 3.14707233 3.06230062 2.74505623 1.65524264 1.11049279] relative max_delta = 4.408739e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0686 3.5353 4.2912 4.4717 4.7589 4.7027 4.5047 4.0166 2.7228 2.1253 relative max_delta = 3.372152e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.6802 7.3128 11.3749 16.9651 18.4132 17.8963 16.6137 14.5181 11.4332 10.3774 relative max_delta = 7.415488e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8490 8.8942 12.0604 16.1534 17.4520 16.8153 15.1827 12.9665 10.1500 9.1401 relative max_delta = 9.061534e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.9141 8.8325 12.0263 15.5697 16.8673 16.2216 14.5780 12.3513 9.5482 8.5378 relative max_delta = 3.647306e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.9125 8.8327 12.0182 15.5108 16.8105 16.1648 14.5211 12.2944 9.4913 8.4809 relative max_delta = 3.500570e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.9125 8.8327 12.0181 15.5103 16.8101 16.1643 14.5207 12.2940 9.4909 8.4805 relative max_delta = 2.981804e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.9125 8.8327 12.0181 15.5103 16.8101 16.1643 14.5207 12.2940 9.4909 8.4805 relative max_delta = 2.236395e-09 Converged to tolerance of 2.236395e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.9125 8.8327 12.0181 15.5103 16.8101 16.1643 14.5207 12.2940 9.4909 8.4805 Final dimensionless free energies f_k = [ 0. 6.91249508 8.83273926 12.01814921 15.51033475 16.81005202 16.16427743 14.52066276 12.29396962 9.49085926 8.48045205] Computing normalized weights... DeltaMij: [[ 0. 4.09452898 5.23196132 7.11879859 9.18735051 9.95722158 9.57470518 8.60113083 7.28217732 5.62179037 5.02328845] [-4.09452898 0. 1.13743234 3.02426961 5.09282152 5.8626926 5.48017619 4.50660184 3.18764834 1.52726139 0.92875947] [-5.23196132 -1.13743234 0. 1.88683727 3.95538918 4.72526026 4.34274385 3.3691695 2.050216 0.38982905 -0.20867287] [-7.11879859 -3.02426961 -1.88683727 0. 2.06855192 2.83842299 2.45590659 1.48233223 0.16337873 -1.49700822 -2.09551014] [-9.18735051 -5.09282152 -3.95538918 -2.06855192 0. 0.76987107 0.38735467 -0.58621968 -1.90517319 -3.56556013 -4.16406206] [-9.95722158 -5.8626926 -4.72526026 -2.83842299 -0.76987107 0. -0.3825164 -1.35609075 -2.67504426 -4.33543121 -4.93393313] [-9.57470518 -5.48017619 -4.34274385 -2.45590659 -0.38735467 0.3825164 0. -0.97357435 -2.29252786 -3.9529148 -4.55141673] [-8.60113083 -4.50660184 -3.3691695 -1.48233223 0.58621968 1.35609075 0.97357435 0. -1.31895351 -2.97934045 -3.57784238] [-7.28217732 -3.18764834 -2.050216 -0.16337873 1.90517319 2.67504426 2.29252786 1.31895351 0. -1.66038695 -2.25888887] [-5.62179037 -1.52726139 -0.38982905 1.49700822 3.56556013 4.33543121 3.9529148 2.97934045 1.66038695 0. -0.59850192] [-5.02328845 -0.92875947 0.20867287 2.09551014 4.16406206 4.93393313 4.55141673 3.57784238 2.25888887 0.59850192 0. ]] dDeltaMij: [[ 0. 0.06044445 0.07459462 0.08607686 0.10289647 0.12502342 0.13459626 0.14842747 0.15840437 0.16442709 0.16669848] [ 0.06044445 0. 0.02505738 0.04864514 0.07449299 0.10292019 0.11435849 0.13035499 0.14161092 0.14831715 0.15083133] [ 0.07459462 0.02505738 0. 0.03315488 0.06567484 0.09672976 0.10882069 0.12552491 0.13717774 0.14409045 0.1466771 ] [ 0.08607686 0.04864514 0.03315488 0. 0.04996842 0.08677065 0.1000727 0.11802155 0.13034691 0.1376032 0.1403095 ] [ 0.10289647 0.07449299 0.06567484 0.04996842 0. 0.05916411 0.07733196 0.09947746 0.11382863 0.12207082 0.12511355] [ 0.12502342 0.10292019 0.09672976 0.08677065 0.05916411 0. 0.03726909 0.07238329 0.09112351 0.10123017 0.10487916] [ 0.13459626 0.11435849 0.10882069 0.1000727 0.07733196 0.03726909 0. 0.04576389 0.0708696 0.08355978 0.08794783] [ 0.14842747 0.13035499 0.12552491 0.11802155 0.09947746 0.07238329 0.04576389 0. 0.03470227 0.05439469 0.06097056] [ 0.15840437 0.14161092 0.13717774 0.13034691 0.11382863 0.09112351 0.0708696 0.03470227 0. 0.02510148 0.03506785] [ 0.16442709 0.14831715 0.14409045 0.1376032 0.12207082 0.10123017 0.08355978 0.05439469 0.02510148 0. 0.01263883] [ 0.16669848 0.15083133 0.1466771 0.1403095 0.12511355 0.10487916 0.08794783 0.06097056 0.03506785 0.01263883 0. ]] Replica 19 / 40 Computing statistical inefficiencies: lambda 0: g = 1.469 lambda 1: g = 2.239 lambda 2: g = 1.623 lambda 3: g = 1.402 lambda 4: g = 1.292 lambda 5: g = 1.672 lambda 6: g = 1.262 lambda 7: g = 1.605 lambda 8: g = 1.736 lambda 9: g = 1.048 lambda 10: g = 1.321 Subsampling data to produce uncorrelated samples... number of samples per lambda: [476 500 365 414 500 500 334 212 299 500 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.6077 +/- 0.5794, Sum=3.9140 +/- 0.1988 Interval 2, DeltaF=1.9346 +/- 0.2424, Sum=5.0599 +/- 0.2019 Interval 3, DeltaF=3.3175 +/- 0.3534, Sum=7.0250 +/- 0.2150 Interval 4, DeltaF=3.5113 +/- 0.4838, Sum=9.1049 +/- 0.2558 Interval 5, DeltaF=0.6761 +/- 0.6798, Sum=9.5054 +/- 0.3747 Interval 6, DeltaF=-0.7087 +/- 0.4053, Sum=9.0856 +/- 0.3871 Interval 7, DeltaF=-1.2909 +/- 0.3468, Sum=8.3209 +/- 0.3936 Interval 8, DeltaF=-2.2108 +/- 0.3870, Sum=7.0114 +/- 0.4035 Interval 9, DeltaF=-3.0909 +/- 0.3016, Sum=5.1806 +/- 0.4071 Interval 10, DeltaF=-1.1016 +/- 0.1700, Sum=4.5280 +/- 0.4074 Forward EXP free energy: 4.5280 +/- 0.4074 Reverse EXP: Interval 1, DeltaF=6.6126 +/- 0.4660, Sum=3.9169 +/- 0.1286 Interval 2, DeltaF=1.8864 +/- 0.2863, Sum=5.0343 +/- 0.1375 Interval 3, DeltaF=3.3857 +/- 0.3681, Sum=7.0398 +/- 0.1592 Interval 4, DeltaF=3.2700 +/- 0.3898, Sum=8.9767 +/- 0.1829 Interval 5, DeltaF=1.1239 +/- 0.4339, Sum=9.6425 +/- 0.2142 Interval 6, DeltaF=-0.5194 +/- 0.3043, Sum=9.3348 +/- 0.2211 Interval 7, DeltaF=-1.5402 +/- 0.3709, Sum=8.4225 +/- 0.2356 Interval 8, DeltaF=-2.3142 +/- 0.3482, Sum=7.0517 +/- 0.2463 Interval 9, DeltaF=-3.0450 +/- 0.2461, Sum=5.2480 +/- 0.2489 Interval 10, DeltaF=-1.1325 +/- 0.1739, Sum=4.5772 +/- 0.2496 Reverse EXP free energy: 4.5772 +/- 0.2496 Averge of forward and reverse EXP: Interval 1, DeltaF=6.6101 +/- 0.2176, Sum=3.9154 +/- 0.0280 Interval 2, DeltaF=1.9105 +/- 0.0549, Sum=5.0471 +/- 0.0281 Interval 3, DeltaF=3.3516 +/- 0.1003, Sum=7.0324 +/- 0.0287 Interval 4, DeltaF=3.3907 +/- 0.1519, Sum=9.0408 +/- 0.0318 Interval 5, DeltaF=0.9000 +/- 0.2716, Sum=9.5739 +/- 0.0540 Interval 6, DeltaF=-0.6141 +/- 0.1026, Sum=9.2102 +/- 0.0544 Interval 7, DeltaF=-1.4156 +/- 0.0994, Sum=8.3717 +/- 0.0547 Interval 8, DeltaF=-2.2625 +/- 0.1049, Sum=7.0315 +/- 0.0551 Interval 9, DeltaF=-3.0680 +/- 0.0595, Sum=5.2143 +/- 0.0551 Interval 10, DeltaF=-1.1171 +/- 0.0228, Sum=4.5526 +/- 0.0551 Average EXP free energy: 4.5526 +/- 0.0551 Interval 1, DeltaF=6.6126 +/- 0.1671, Sum=3.9169 +/- 0.0165 Interval 2, DeltaF=1.9346 +/- 0.3682, Sum=5.0628 +/- 0.0820 Interval 3, DeltaF=3.3857 +/- 0.2733, Sum=7.0683 +/- 0.0932 Interval 4, DeltaF=3.5113 +/- 0.4342, Sum=9.1482 +/- 0.1454 Interval 5, DeltaF=1.1239 +/- 0.3659, Sum=9.8140 +/- 0.1656 Interval 6, DeltaF=-0.7087 +/- 0.7000, Sum=9.3942 +/- 0.3342 Interval 7, DeltaF=-1.5402 +/- 0.4198, Sum=8.4818 +/- 0.3501 Interval 8, DeltaF=-2.2108 +/- 0.7324, Sum=7.1723 +/- 0.4728 Interval 9, DeltaF=-3.0450 +/- 0.4550, Sum=5.3686 +/- 0.4884 Interval 10, DeltaF=-1.1016 +/- 0.7483, Sum=4.7161 +/- 0.5904 Double-Wide EXP free energy: 4.7161 +/- 0.5904 Method: BAR Interval 1, DeltaF=6.7621 +/- 0.2984, Sum=4.0055 +/- 0.0527 Interval 2, DeltaF=1.9019 +/- 0.2026, Sum=5.1320 +/- 0.0581 Interval 3, DeltaF=3.1916 +/- 0.2625, Sum=7.0225 +/- 0.0710 Interval 4, DeltaF=3.2268 +/- 0.2898, Sum=8.9339 +/- 0.0867 Interval 5, DeltaF=1.0434 +/- 0.3171, Sum=9.5519 +/- 0.1052 Interval 6, DeltaF=-0.5218 +/- 0.2291, Sum=9.2428 +/- 0.1097 Interval 7, DeltaF=-1.5230 +/- 0.2765, Sum=8.3407 +/- 0.1186 Interval 8, DeltaF=-2.3053 +/- 0.2534, Sum=6.9752 +/- 0.1246 Interval 9, DeltaF=-2.9900 +/- 0.2020, Sum=5.2041 +/- 0.1269 Interval 10, DeltaF=-1.1129 +/- 0.1354, Sum=4.5449 +/- 0.1274 BAR free energy: 4.5449 +/- 0.1274 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.6158 +/- 0.4461, Sum=3.9188 +/- 0.1179 Interval 2, DeltaF=1.9054 +/- 0.2854, Sum=5.0474 +/- 0.1274 Interval 3, DeltaF=3.1249 +/- 0.3306, Sum=6.8984 +/- 0.1429 Interval 4, DeltaF=3.1081 +/- 0.3523, Sum=8.7395 +/- 0.1607 Interval 5, DeltaF=0.9846 +/- 0.3407, Sum=9.3226 +/- 0.1748 Interval 6, DeltaF=-0.5198 +/- 0.2145, Sum=9.0147 +/- 0.1769 Interval 7, DeltaF=-1.5363 +/- 0.2510, Sum=8.1047 +/- 0.1808 Interval 8, DeltaF=-2.3280 +/- 0.3516, Sum=6.7258 +/- 0.1950 Interval 9, DeltaF=-3.0126 +/- 0.3926, Sum=4.9413 +/- 0.2153 Interval 10, DeltaF=-1.1220 +/- 0.1983, Sum=4.2767 +/- 0.2166 Unopt. BAR free energy: 4.2767 +/- 0.2166 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7640 +/- 0.2995, Sum=4.0065 +/- 0.0531 Interval 2, DeltaF=1.9022 +/- 0.2012, Sum=5.1333 +/- 0.0583 Interval 3, DeltaF=3.1805 +/- 0.2629, Sum=7.0172 +/- 0.0712 Interval 4, DeltaF=3.2200 +/- 0.2943, Sum=8.9245 +/- 0.0878 Interval 5, DeltaF=1.0414 +/- 0.3182, Sum=9.5414 +/- 0.1063 Interval 6, DeltaF=-0.5292 +/- 0.2473, Sum=9.2279 +/- 0.1123 Interval 7, DeltaF=-1.5157 +/- 0.2919, Sum=8.3301 +/- 0.1231 Interval 8, DeltaF=-2.3128 +/- 0.2594, Sum=6.9602 +/- 0.1294 Interval 9, DeltaF=-2.9901 +/- 0.2015, Sum=5.1891 +/- 0.1316 Interval 10, DeltaF=-1.1139 +/- 0.1368, Sum=4.5293 +/- 0.1321 Postopt. BAR free energy: 4.5293 +/- 0.1321 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 976 N_k = [476 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.52078399] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.81332093] relative max_delta = 2.685333e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0029 relative max_delta = 3.788725e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7103 relative max_delta = 2.544550e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7621 relative max_delta = 7.649826e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7621 relative max_delta = 8.859550e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7621 relative max_delta = 1.172025e-11 Converged to tolerance of 1.172025e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7621 Final dimensionless free energies f_k = [ 0. 6.76213549] Computing normalized weights... Interval 1, DeltaF=6.7621 +/- 0.2984, Sum=4.0055 +/- 0.0527 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 865 N_k = [500 365] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.47894176] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.79354382] relative max_delta = 1.754081e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8044 relative max_delta = 6.034754e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9023 relative max_delta = 5.145559e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9019 relative max_delta = 2.424109e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9019 relative max_delta = 4.572955e-09 Converged to tolerance of 4.572955e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9019 Final dimensionless free energies f_k = [ 0. 1.90185698] Computing normalized weights... Interval 2, DeltaF=1.9019 +/- 0.2026, Sum=5.1320 +/- 0.0581 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 779 N_k = [365 414] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.6112483] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.41662693] relative max_delta = 3.332656e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4960 relative max_delta = 3.181406e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2055 relative max_delta = 2.213282e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1916 relative max_delta = 4.368650e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1916 relative max_delta = 1.075219e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1916 relative max_delta = 4.174344e-16 Converged to tolerance of 4.174344e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1916 Final dimensionless free energies f_k = [ 0. 3.19156135] Computing normalized weights... Interval 3, DeltaF=3.1916 +/- 0.2625, Sum=7.0225 +/- 0.0710 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 914 N_k = [414 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.98304092] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.70396312] relative max_delta = 4.230856e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8787 relative max_delta = 9.299781e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.4015 relative max_delta = 4.476908e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2293 relative max_delta = 5.332827e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2268 relative max_delta = 7.534761e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2268 relative max_delta = 1.522300e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.2268 relative max_delta = 7.844521e-15 Converged to tolerance of 7.844521e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2268 Final dimensionless free energies f_k = [ 0. 3.22684888] Computing normalized weights... Interval 4, DeltaF=3.2268 +/- 0.2898, Sum=8.9339 +/- 0.0867 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.26676471] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.47005971] relative max_delta = 4.324876e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5310 relative max_delta = 1.148168e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.0726 relative max_delta = 5.049060e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0435 relative max_delta = 2.789703e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0434 relative max_delta = 9.296414e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0434 relative max_delta = 1.025339e-09 Converged to tolerance of 1.025339e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0434 Final dimensionless free energies f_k = [ 0. 1.04337919] Computing normalized weights... Interval 5, DeltaF=1.0434 +/- 0.3171, Sum=9.5519 +/- 0.1052 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 834 N_k = [500 334] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.34403258] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.45945359] relative max_delta = 2.512136e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4657 relative max_delta = 1.330717e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5215 relative max_delta = 1.070816e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5218 relative max_delta = 6.204951e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5218 relative max_delta = 2.133094e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5218 relative max_delta = 2.553136e-15 Converged to tolerance of 2.553136e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5218 Final dimensionless free energies f_k = [ 0. -0.52181607] Computing normalized weights... Interval 6, DeltaF=-0.5218 +/- 0.2291, Sum=9.2428 +/- 0.1097 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 546 N_k = [334 212] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.92775699] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.27375633] relative max_delta = 2.716370e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.2981 relative max_delta = 1.879079e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5186 relative max_delta = 1.451837e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5230 relative max_delta = 2.857830e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5230 relative max_delta = 1.170823e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5230 relative max_delta = 1.968243e-13 Converged to tolerance of 1.968243e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5230 Final dimensionless free energies f_k = [ 0. -1.52298412] Computing normalized weights... Interval 7, DeltaF=-1.5230 +/- 0.2765, Sum=8.3407 +/- 0.1186 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 511 N_k = [212 299] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.65042458] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.08986816] relative max_delta = 2.102734e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1117 relative max_delta = 1.031901e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3073 relative max_delta = 8.477324e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3053 relative max_delta = 8.460929e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3053 relative max_delta = 6.871781e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3053 relative max_delta = 9.631914e-16 Converged to tolerance of 9.631914e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3053 Final dimensionless free energies f_k = [ 0. -2.30530093] Computing normalized weights... Interval 8, DeltaF=-2.3053 +/- 0.2534, Sum=6.9752 +/- 0.1246 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 799 N_k = [299 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.35161311] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.83719808] relative max_delta = 1.711495e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8528 relative max_delta = 5.452646e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9922 relative max_delta = 4.660192e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9900 relative max_delta = 7.297072e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9900 relative max_delta = 1.657740e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9900 relative max_delta = 8.762927e-15 Converged to tolerance of 8.762927e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9900 Final dimensionless free energies f_k = [ 0. -2.99001285] Computing normalized weights... Interval 9, DeltaF=-2.9900 +/- 0.2020, Sum=5.2041 +/- 0.1269 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.02778322] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.10629198] relative max_delta = 7.096568e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.1070 relative max_delta = 5.979703e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.1129 relative max_delta = 5.352889e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.1129 relative max_delta = 1.418543e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.1129 relative max_delta = 4.588890e-15 Converged to tolerance of 4.588890e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.1129 Final dimensionless free energies f_k = [ 0. -1.11291104] Computing normalized weights... Interval 10, DeltaF=-1.1129 +/- 0.1354, Sum=4.5449 +/- 0.1274 Pairwise MBAR free energy: 4.5449 +/- 0.1274 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4600 N_k = [476 500 365 414 500 500 334 212 299 500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.0107287 1.9917555 1.70639143 1.51047353 1.57754333 1.60078205 1.67434221 1.67912098 1.01973348 0.46142793] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.99635214 3.3287184 3.11729993 2.8044242 2.90714731 2.92956 2.94959912 2.78349798 1.62835143 0.88440601] relative max_delta = 4.238594e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2698 3.7377 4.0615 4.2465 4.4606 4.4392 4.3572 4.0209 2.6428 1.8563 relative max_delta = 3.482664e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8669 7.5999 12.0784 16.4231 17.6064 17.1785 16.1070 14.1236 10.7804 9.6245 relative max_delta = 7.466466e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7432 8.8001 11.9397 15.4541 16.5231 16.0194 14.4886 12.2180 9.2078 8.0926 relative max_delta = 1.153319e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7664 8.6944 11.9020 15.1705 16.2385 15.7253 14.1740 11.8742 8.8936 7.7778 relative max_delta = 2.117241e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7657 8.6932 11.8999 15.1628 16.2310 15.7177 14.1664 11.8663 8.8860 7.7702 relative max_delta = 4.833568e-04 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7657 8.6932 11.8999 15.1628 16.2310 15.7177 14.1664 11.8663 8.8860 7.7702 relative max_delta = 3.118924e-07 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7657 8.6932 11.8999 15.1628 16.2310 15.7177 14.1664 11.8663 8.8860 7.7702 relative max_delta = 1.659145e-13 Converged to tolerance of 1.659145e-13 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7657 8.6932 11.8999 15.1628 16.2310 15.7177 14.1664 11.8663 8.8860 7.7702 Final dimensionless free energies f_k = [ 0. 6.76569469 8.69320591 11.89986938 15.16276788 16.23099099 15.71770425 14.16640267 11.86633439 8.8859929 7.77020452] Computing normalized weights... DeltaMij: [[ 0. 4.00757363 5.14931051 7.04873704 8.98147367 9.61422211 9.3101832 8.39128934 7.028873 5.26350544 4.60258232] [-4.00757363 0. 1.14173688 3.04116341 4.97390004 5.60664848 5.30260957 4.38371572 3.02129938 1.25593181 0.59500869] [-5.14931051 -1.14173688 0. 1.89942653 3.83216316 4.4649116 4.16087269 3.24197884 1.8795625 0.11419493 -0.54672819] [-7.04873704 -3.04116341 -1.89942653 0. 1.93273663 2.56548507 2.26144617 1.34255231 -0.01986403 -1.78523159 -2.44615472] [-8.98147367 -4.97390004 -3.83216316 -1.93273663 0. 0.63274844 0.32870953 -0.59018432 -1.95260066 -3.71796823 -4.37889135] [-9.61422211 -5.60664848 -4.4649116 -2.56548507 -0.63274844 0. -0.30403891 -1.22293277 -2.5853491 -4.35071667 -5.01163979] [-9.3101832 -5.30260957 -4.16087269 -2.26144617 -0.32870953 0.30403891 0. -0.91889386 -2.2813102 -4.04667776 -4.70760088] [-8.39128934 -4.38371572 -3.24197884 -1.34255231 0.59018432 1.22293277 0.91889386 0. -1.36241634 -3.1277839 -3.78870703] [-7.028873 -3.02129938 -1.8795625 0.01986403 1.95260066 2.5853491 2.2813102 1.36241634 0. -1.76536756 -2.42629069] [-5.26350544 -1.25593181 -0.11419493 1.78523159 3.71796823 4.35071667 4.04667776 3.1277839 1.76536756 0. -0.66092312] [-4.60258232 -0.59500869 0.54672819 2.44615472 4.37889135 5.01163979 4.70760088 3.78870703 2.42629069 0.66092312 0. ]] dDeltaMij: [[ 0. 0.05171072 0.06413279 0.0778968 0.0957174 0.11676693 0.1243912 0.1361373 0.1465225 0.15186748 0.15343508] [ 0.05171072 0. 0.0224422 0.04867056 0.0739657 0.09971858 0.10854698 0.12183038 0.13333462 0.13918695 0.14089571] [ 0.06413279 0.0224422 0. 0.03536186 0.06630272 0.09417588 0.10347824 0.11733687 0.12924171 0.13527124 0.13702883] [ 0.0778968 0.04867056 0.03536186 0. 0.0483456 0.0824727 0.09295444 0.10816982 0.12098012 0.12740125 0.12926589] [ 0.0957174 0.0739657 0.06630272 0.0483456 0. 0.0576066 0.07177951 0.09062552 0.10558611 0.1128863 0.11498656] [ 0.11676693 0.09971858 0.09417588 0.0824727 0.0576066 0. 0.02955513 0.06228803 0.08258283 0.09173054 0.09430305] [ 0.1243912 0.10854698 0.10347824 0.09295444 0.07177951 0.02955513 0. 0.04266698 0.06828938 0.07915931 0.08212752] [ 0.1361373 0.12183038 0.11733687 0.10816982 0.09062552 0.06228803 0.04266698 0. 0.03440122 0.05094879 0.05549408] [ 0.1465225 0.13333462 0.12924171 0.12098012 0.10558611 0.08258283 0.06828938 0.03440122 0. 0.02140977 0.02894685] [ 0.15186748 0.13918695 0.13527124 0.12740125 0.1128863 0.09173054 0.07915931 0.05094879 0.02140977 0. 0.00996933] [ 0.15343508 0.14089571 0.13702883 0.12926589 0.11498656 0.09430305 0.08212752 0.05549408 0.02894685 0.00996933 0. ]] Replica 20 / 40 Computing statistical inefficiencies: lambda 0: g = 1.729 lambda 1: g = 1.375 lambda 2: g = 1.103 lambda 3: g = 2.023 lambda 4: g = 1.194 lambda 5: g = 2.226 lambda 6: g = 1.690 lambda 7: g = 1.634 lambda 8: g = 1.245 lambda 9: g = 1.529 lambda 10: g = 2.079 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 334 500 500 500 370 234 332 188 364 349] Method: EXP Forward EXP: Interval 1, DeltaF=6.7931 +/- 0.4368, Sum=4.0238 +/- 0.1130 Interval 2, DeltaF=2.0113 +/- 0.2532, Sum=5.2151 +/- 0.1192 Interval 3, DeltaF=3.3359 +/- 0.4729, Sum=7.1911 +/- 0.1782 Interval 4, DeltaF=3.8974 +/- 0.3970, Sum=9.4997 +/- 0.2012 Interval 5, DeltaF=2.0927 +/- 0.4475, Sum=10.7393 +/- 0.2335 Interval 6, DeltaF=-0.3735 +/- 0.3539, Sum=10.5180 +/- 0.2450 Interval 7, DeltaF=-1.5806 +/- 0.4052, Sum=9.5818 +/- 0.2636 Interval 8, DeltaF=-2.3219 +/- 0.3458, Sum=8.2064 +/- 0.2730 Interval 9, DeltaF=-2.8523 +/- 0.2941, Sum=6.5169 +/- 0.2778 Interval 10, DeltaF=-1.1142 +/- 0.1728, Sum=5.8569 +/- 0.2783 Forward EXP free energy: 5.8569 +/- 0.2783 Reverse EXP: Interval 1, DeltaF=7.2016 +/- 0.6386, Sum=4.2658 +/- 0.2415 Interval 2, DeltaF=2.0346 +/- 0.3297, Sum=5.4710 +/- 0.2500 Interval 3, DeltaF=2.9215 +/- 0.3154, Sum=7.2015 +/- 0.2568 Interval 4, DeltaF=3.2928 +/- 0.3733, Sum=9.1519 +/- 0.2698 Interval 5, DeltaF=1.1837 +/- 0.4422, Sum=9.8531 +/- 0.2936 Interval 6, DeltaF=-0.5503 +/- 0.3211, Sum=9.5271 +/- 0.2999 Interval 7, DeltaF=-1.7470 +/- 0.3197, Sum=8.4923 +/- 0.3059 Interval 8, DeltaF=-2.1319 +/- 0.3655, Sum=7.2295 +/- 0.3160 Interval 9, DeltaF=-2.9475 +/- 0.3785, Sum=5.4836 +/- 0.3272 Interval 10, DeltaF=-1.1072 +/- 0.1868, Sum=4.8278 +/- 0.3278 Reverse EXP free energy: 4.8278 +/- 0.3278 Averge of forward and reverse EXP: Interval 1, DeltaF=6.9974 +/- 0.2450, Sum=4.1448 +/- 0.0356 Interval 2, DeltaF=2.0229 +/- 0.0687, Sum=5.3431 +/- 0.0357 Interval 3, DeltaF=3.1287 +/- 0.1332, Sum=7.1963 +/- 0.0372 Interval 4, DeltaF=3.5951 +/- 0.1145, Sum=9.3258 +/- 0.0380 Interval 5, DeltaF=1.6382 +/- 0.1523, Sum=10.2962 +/- 0.0404 Interval 6, DeltaF=-0.4619 +/- 0.0883, Sum=10.0226 +/- 0.0407 Interval 7, DeltaF=-1.6638 +/- 0.1052, Sum=9.0371 +/- 0.0412 Interval 8, DeltaF=-2.2269 +/- 0.0976, Sum=7.7180 +/- 0.0416 Interval 9, DeltaF=-2.8999 +/- 0.0911, Sum=6.0003 +/- 0.0419 Interval 10, DeltaF=-1.1107 +/- 0.0250, Sum=5.3423 +/- 0.0419 Average EXP free energy: 5.3423 +/- 0.0419 Interval 1, DeltaF=7.2016 +/- 0.3138, Sum=4.2658 +/- 0.0583 Interval 2, DeltaF=2.0113 +/- 0.2134, Sum=5.4572 +/- 0.0643 Interval 3, DeltaF=2.9215 +/- 0.4657, Sum=7.1876 +/- 0.1436 Interval 4, DeltaF=3.8974 +/- 0.3492, Sum=9.4962 +/- 0.1608 Interval 5, DeltaF=1.1837 +/- 0.5180, Sum=10.1973 +/- 0.2261 Interval 6, DeltaF=-0.3735 +/- 0.4398, Sum=9.9761 +/- 0.2535 Interval 7, DeltaF=-1.7470 +/- 0.5566, Sum=8.9413 +/- 0.3129 Interval 8, DeltaF=-2.3219 +/- 0.4931, Sum=7.5659 +/- 0.3445 Interval 9, DeltaF=-2.9475 +/- 0.5910, Sum=5.8200 +/- 0.4018 Interval 10, DeltaF=-1.1142 +/- 0.5109, Sum=5.1600 +/- 0.4305 Double-Wide EXP free energy: 5.1600 +/- 0.4305 Method: BAR Interval 1, DeltaF=6.6338 +/- 0.3050, Sum=3.9294 +/- 0.0551 Interval 2, DeltaF=1.9765 +/- 0.2001, Sum=5.1002 +/- 0.0600 Interval 3, DeltaF=3.1943 +/- 0.2498, Sum=6.9923 +/- 0.0705 Interval 4, DeltaF=3.3075 +/- 0.2798, Sum=8.9515 +/- 0.0843 Interval 5, DeltaF=1.3731 +/- 0.3190, Sum=9.7648 +/- 0.1037 Interval 6, DeltaF=-0.5450 +/- 0.2528, Sum=9.4420 +/- 0.1104 Interval 7, DeltaF=-1.6516 +/- 0.2710, Sum=8.4637 +/- 0.1186 Interval 8, DeltaF=-2.2754 +/- 0.2484, Sum=7.1159 +/- 0.1241 Interval 9, DeltaF=-2.9364 +/- 0.2305, Sum=5.3766 +/- 0.1281 Interval 10, DeltaF=-1.1130 +/- 0.1467, Sum=4.7173 +/- 0.1287 BAR free energy: 4.7173 +/- 0.1287 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.7712 +/- 0.5475, Sum=4.0108 +/- 0.1775 Interval 2, DeltaF=1.9753 +/- 0.2340, Sum=5.1809 +/- 0.1805 Interval 3, DeltaF=3.3082 +/- 0.3173, Sum=7.1404 +/- 0.1901 Interval 4, DeltaF=3.3451 +/- 0.3591, Sum=9.1219 +/- 0.2049 Interval 5, DeltaF=1.3735 +/- 0.3686, Sum=9.9354 +/- 0.2201 Interval 6, DeltaF=-0.5439 +/- 0.2357, Sum=9.6132 +/- 0.2226 Interval 7, DeltaF=-1.6732 +/- 0.3021, Sum=8.6222 +/- 0.2290 Interval 8, DeltaF=-2.1936 +/- 0.2647, Sum=7.3228 +/- 0.2328 Interval 9, DeltaF=-2.9695 +/- 0.4368, Sum=5.5639 +/- 0.2587 Interval 10, DeltaF=-1.1092 +/- 0.2122, Sum=4.9068 +/- 0.2601 Unopt. BAR free energy: 4.9068 +/- 0.2601 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6368 +/- 0.3038, Sum=3.9312 +/- 0.0547 Interval 2, DeltaF=1.9767 +/- 0.2009, Sum=5.1021 +/- 0.0597 Interval 3, DeltaF=3.2022 +/- 0.2512, Sum=6.9989 +/- 0.0704 Interval 4, DeltaF=3.3089 +/- 0.2873, Sum=8.9589 +/- 0.0857 Interval 5, DeltaF=1.3790 +/- 0.3329, Sum=9.7757 +/- 0.1080 Interval 6, DeltaF=-0.5434 +/- 0.2716, Sum=9.4538 +/- 0.1165 Interval 7, DeltaF=-1.6533 +/- 0.2727, Sum=8.4745 +/- 0.1245 Interval 8, DeltaF=-2.2679 +/- 0.2408, Sum=7.1311 +/- 0.1292 Interval 9, DeltaF=-2.9354 +/- 0.2270, Sum=5.3924 +/- 0.1327 Interval 10, DeltaF=-1.1127 +/- 0.1474, Sum=4.7333 +/- 0.1334 Postopt. BAR free energy: 4.7333 +/- 0.1334 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 834 N_k = [500 334] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.80896651] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.99257917] relative max_delta = 2.370744e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1639 relative max_delta = 3.318130e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6876 relative max_delta = 2.278404e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6338 relative max_delta = 8.110428e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6338 relative max_delta = 6.549656e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6338 relative max_delta = 4.350256e-12 Converged to tolerance of 4.350256e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6338 Final dimensionless free energies f_k = [ 0. 6.63379257] Computing normalized weights... Interval 1, DeltaF=6.6338 +/- 0.3050, Sum=3.9294 +/- 0.0551 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 834 N_k = [334 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53669027] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.87034721] relative max_delta = 1.783930e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8809 relative max_delta = 5.604220e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9759 relative max_delta = 4.808311e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9765 relative max_delta = 3.241198e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9765 relative max_delta = 1.620751e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.9765 relative max_delta = 1.123403e-15 Converged to tolerance of 1.123403e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9765 Final dimensionless free energies f_k = [ 0. 1.97653598] Computing normalized weights... Interval 2, DeltaF=1.9765 +/- 0.2001, Sum=5.1002 +/- 0.0600 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.57012128] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.37135268] relative max_delta = 3.378795e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4572 relative max_delta = 3.491902e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2209 relative max_delta = 2.371261e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1944 relative max_delta = 8.313062e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1943 relative max_delta = 5.180247e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1943 relative max_delta = 2.086743e-12 Converged to tolerance of 2.086743e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1943 Final dimensionless free energies f_k = [ 0. 3.19434614] Computing normalized weights... Interval 3, DeltaF=3.1943 +/- 0.2498, Sum=6.9923 +/- 0.0705 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.99452052] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.73593943] relative max_delta = 4.270995e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9265 relative max_delta = 9.891326e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5612 relative max_delta = 4.590308e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3136 relative max_delta = 7.472943e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3075 relative max_delta = 1.827965e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3075 relative max_delta = 1.122652e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3075 relative max_delta = 4.230736e-13 Converged to tolerance of 4.230736e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3075 Final dimensionless free energies f_k = [ 0. 3.30752142] Computing normalized weights... Interval 4, DeltaF=3.3075 +/- 0.2798, Sum=8.9515 +/- 0.0843 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 870 N_k = [500 370] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.36007892] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.63731135] relative max_delta = 4.350031e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7203 relative max_delta = 1.152683e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.4470 relative max_delta = 5.021932e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3739 relative max_delta = 5.319753e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3731 relative max_delta = 6.322647e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3731 relative max_delta = 8.819115e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3731 relative max_delta = 1.940558e-15 Converged to tolerance of 1.940558e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3731 Final dimensionless free energies f_k = [ 0. 1.37307701] Computing normalized weights... Interval 5, DeltaF=1.3731 +/- 0.3190, Sum=9.7648 +/- 0.1037 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 604 N_k = [370 234] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.35145937] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.4744674] relative max_delta = 2.592550e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4815 relative max_delta = 1.453955e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5446 relative max_delta = 1.158722e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5450 relative max_delta = 7.853972e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5450 relative max_delta = 3.697588e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5450 relative max_delta = 4.074242e-15 Converged to tolerance of 4.074242e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5450 Final dimensionless free energies f_k = [ 0. -0.54499605] Computing normalized weights... Interval 6, DeltaF=-0.5450 +/- 0.2528, Sum=9.4420 +/- 0.1104 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 566 N_k = [234 332] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.05629259] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.4106223] relative max_delta = 2.511868e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4348 relative max_delta = 1.682389e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6519 relative max_delta = 1.314394e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6516 relative max_delta = 1.435232e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6516 relative max_delta = 1.635482e-10 Converged to tolerance of 1.635482e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6516 Final dimensionless free energies f_k = [ 0. -1.65164612] Computing normalized weights... Interval 7, DeltaF=-1.6516 +/- 0.2710, Sum=8.4637 +/- 0.1186 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 520 N_k = [332 188] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.58877674] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.05715201] relative max_delta = 2.276814e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0787 relative max_delta = 1.034536e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2727 relative max_delta = 8.539866e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2754 relative max_delta = 1.158938e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2754 relative max_delta = 2.429903e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2754 relative max_delta = 1.190544e-14 Converged to tolerance of 1.190544e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2754 Final dimensionless free energies f_k = [ 0. -2.27538349] Computing normalized weights... Interval 8, DeltaF=-2.2754 +/- 0.2484, Sum=7.1159 +/- 0.1241 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 552 N_k = [188 364] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.24801462] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.75641878] relative max_delta = 1.844437e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7749 relative max_delta = 6.649319e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9400 relative max_delta = 5.616719e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9364 relative max_delta = 1.240759e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9364 relative max_delta = 5.744081e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9364 relative max_delta = 1.232591e-13 Converged to tolerance of 1.232591e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9364 Final dimensionless free energies f_k = [ 0. -2.93635638] Computing normalized weights... Interval 9, DeltaF=-2.9364 +/- 0.2305, Sum=5.3766 +/- 0.1281 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 713 N_k = [364 349] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.0275407] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.10643434] relative max_delta = 7.130440e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.1071 relative max_delta = 5.907142e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.1130 relative max_delta = 5.288335e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.1130 relative max_delta = 1.115459e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.1130 relative max_delta = 3.192090e-15 Converged to tolerance of 3.192090e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.1130 Final dimensionless free energies f_k = [ 0. -1.11297422] Computing normalized weights... Interval 10, DeltaF=-1.1130 +/- 0.1467, Sum=4.7173 +/- 0.1287 Pairwise MBAR free energy: 4.7173 +/- 0.1287 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4171 N_k = [500 334 500 500 500 370 234 332 188 364 349] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89734755 1.85120386 1.6682105 1.48581874 1.70657358 1.68957055 1.65146509 1.51078954 0.836899 0.38096433] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.77873731 3.08403668 3.05425786 2.7909004 3.11942853 3.07878543 2.91591764 2.53046222 1.3707711 0.72286997] relative max_delta = 4.529211e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0367 3.4796 3.9004 4.1885 4.6449 4.5577 4.2748 3.7158 2.3528 1.6556 relative max_delta = 3.284167e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.4962 7.2156 11.2568 16.0838 17.6337 17.1234 15.7187 13.5352 10.3612 9.2287 relative max_delta = 7.365896e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6040 8.6195 11.7818 15.4332 16.8038 16.2426 14.6288 12.3356 9.3770 8.2729 relative max_delta = 8.354340e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6400 8.5888 11.7589 15.0694 16.4326 15.8685 14.2527 11.9497 9.0020 7.8978 relative max_delta = 2.347888e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6394 8.5888 11.7553 15.0514 16.4151 15.8510 14.2351 11.9322 8.9845 7.8803 relative max_delta = 1.095395e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6394 8.5888 11.7553 15.0514 16.4150 15.8510 14.2351 11.9322 8.9845 7.8803 relative max_delta = 2.148140e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6394 8.5888 11.7553 15.0514 16.4150 15.8510 14.2351 11.9322 8.9845 7.8803 relative max_delta = 8.590662e-12 Converged to tolerance of 8.590662e-12 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6394 8.5888 11.7553 15.0514 16.4150 15.8510 14.2351 11.9322 8.9845 7.8803 Final dimensionless free energies f_k = [ 0. 6.63937315 8.58884245 11.75528092 15.05137745 16.41504368 15.85097405 14.23511579 11.9321542 8.98447068 7.88025383] Computing normalized weights... DeltaMij: [[ 0. 3.93274867 5.08749214 6.96309189 8.91549295 9.72324339 9.38912388 8.43199069 7.06786054 5.32183751 4.66776863] [-3.93274867 0. 1.15474347 3.03034322 4.98274429 5.79049472 5.45637522 4.49924203 3.13511187 1.38908884 0.73501996] [-5.08749214 -1.15474347 0. 1.87559975 3.82800082 4.63575125 4.30163175 3.34449856 1.9803684 0.23434537 -0.41972351] [-6.96309189 -3.03034322 -1.87559975 0. 1.95240107 2.7601515 2.426032 1.4688988 0.10476865 -1.64125438 -2.29532326] [-8.91549295 -4.98274429 -3.82800082 -1.95240107 0. 0.80775043 0.47363093 -0.48350226 -1.84763242 -3.59365545 -4.24772432] [-9.72324339 -5.79049472 -4.63575125 -2.7601515 -0.80775043 0. -0.3341195 -1.2912527 -2.65538285 -4.40140588 -5.05547476] [-9.38912388 -5.45637522 -4.30163175 -2.426032 -0.47363093 0.3341195 0. -0.95713319 -2.32126335 -4.06728638 -4.72135525] [-8.43199069 -4.49924203 -3.34449856 -1.4688988 0.48350226 1.2912527 0.95713319 0. -1.36413016 -3.11015319 -3.76422206] [-7.06786054 -3.13511187 -1.9803684 -0.10476865 1.84763242 2.65538285 2.32126335 1.36413016 0. -1.74602303 -2.40009191] [-5.32183751 -1.38908884 -0.23434537 1.64125438 3.59365545 4.40140588 4.06728638 3.11015319 1.74602303 0. -0.65406888] [-4.66776863 -0.73501996 0.41972351 2.29532326 4.24772432 5.05547476 4.72135525 3.76422206 2.40009191 0.65406888 0. ]] dDeltaMij: [[ 0. 0.05292901 0.06667747 0.07912195 0.09490893 0.11654957 0.12718306 0.13916418 0.14810619 0.15425919 0.15650837] [ 0.05292901 0. 0.02257889 0.04703912 0.07048235 0.09769335 0.11016223 0.12380168 0.13377455 0.14055634 0.14302118] [ 0.06667747 0.02257889 0. 0.03379989 0.06268585 0.09222699 0.10534487 0.11953527 0.12983626 0.13681341 0.13934447] [ 0.07912195 0.04703912 0.03379989 0. 0.04551144 0.08147957 0.09607696 0.11145361 0.12243644 0.12981192 0.13247682] [ 0.09490893 0.07048235 0.06268585 0.04551144 0. 0.05868658 0.07765279 0.09603018 0.10858427 0.1168375 0.11979138] [ 0.11654957 0.09769335 0.09222699 0.08147957 0.05868658 0. 0.03530883 0.0660049 0.08323896 0.0937479 0.09740441] [ 0.12718306 0.11016223 0.10534487 0.09607696 0.07765279 0.03530883 0. 0.04105565 0.06463411 0.07779518 0.08216621] [ 0.13916418 0.12380168 0.11953527 0.11145361 0.09603018 0.0660049 0.04105565 0. 0.03323715 0.05302255 0.05927261] [ 0.14810619 0.13377455 0.12983626 0.12243644 0.10858427 0.08323896 0.06463411 0.03323715 0. 0.024916 0.03420158] [ 0.15425919 0.14055634 0.13681341 0.12981192 0.1168375 0.0937479 0.07779518 0.05302255 0.024916 0. 0.01177052] [ 0.15650837 0.14302118 0.13934447 0.13247682 0.11979138 0.09740441 0.08216621 0.05927261 0.03420158 0.01177052 0. ]] Replica 21 / 40 Computing statistical inefficiencies: lambda 0: g = 2.657 lambda 1: g = 1.780 lambda 2: g = 1.217 lambda 3: g = 1.446 lambda 4: g = 1.843 lambda 5: g = 2.447 lambda 6: g = 1.612 lambda 7: g = 2.509 lambda 8: g = 1.376 lambda 9: g = 2.030 lambda 10: g = 1.479 Subsampling data to produce uncorrelated samples... number of samples per lambda: [441 500 490 336 373 345 418 163 234 310 408] Method: EXP Forward EXP: Interval 1, DeltaF=7.0248 +/- 0.4964, Sum=4.1610 +/- 0.1460 Interval 2, DeltaF=1.8503 +/- 0.2545, Sum=5.2570 +/- 0.1509 Interval 3, DeltaF=3.5693 +/- 0.3030, Sum=7.3713 +/- 0.1604 Interval 4, DeltaF=4.1549 +/- 0.3702, Sum=9.8324 +/- 0.1798 Interval 5, DeltaF=1.7070 +/- 0.5229, Sum=10.8435 +/- 0.2420 Interval 6, DeltaF=-0.6630 +/- 0.4922, Sum=10.4508 +/- 0.2813 Interval 7, DeltaF=-1.7570 +/- 0.4191, Sum=9.4100 +/- 0.3000 Interval 8, DeltaF=-2.3227 +/- 0.3616, Sum=8.0342 +/- 0.3098 Interval 9, DeltaF=-2.7997 +/- 0.2971, Sum=6.3758 +/- 0.3142 Interval 10, DeltaF=-1.0974 +/- 0.1798, Sum=5.7258 +/- 0.3148 Forward EXP free energy: 5.7258 +/- 0.3148 Reverse EXP: Interval 1, DeltaF=6.4712 +/- 0.4244, Sum=3.8331 +/- 0.1067 Interval 2, DeltaF=1.9166 +/- 0.2660, Sum=4.9684 +/- 0.1146 Interval 3, DeltaF=3.0794 +/- 0.3622, Sum=6.7925 +/- 0.1385 Interval 4, DeltaF=3.3994 +/- 0.3781, Sum=8.8061 +/- 0.1623 Interval 5, DeltaF=0.8209 +/- 0.4862, Sum=9.2923 +/- 0.2144 Interval 6, DeltaF=-0.4417 +/- 0.2743, Sum=9.0307 +/- 0.2189 Interval 7, DeltaF=-1.7373 +/- 0.4394, Sum=8.0017 +/- 0.2470 Interval 8, DeltaF=-2.1873 +/- 0.3427, Sum=6.7060 +/- 0.2566 Interval 9, DeltaF=-3.0414 +/- 0.2747, Sum=4.9045 +/- 0.2605 Interval 10, DeltaF=-1.0507 +/- 0.1879, Sum=4.2822 +/- 0.2613 Reverse EXP free energy: 4.2822 +/- 0.2613 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7480 +/- 0.1661, Sum=3.9971 +/- 0.0163 Interval 2, DeltaF=1.8835 +/- 0.0522, Sum=5.1127 +/- 0.0164 Interval 3, DeltaF=3.3244 +/- 0.0871, Sum=7.0819 +/- 0.0170 Interval 4, DeltaF=3.7772 +/- 0.1078, Sum=9.3192 +/- 0.0184 Interval 5, DeltaF=1.2639 +/- 0.1967, Sum=10.0679 +/- 0.0294 Interval 6, DeltaF=-0.5524 +/- 0.1380, Sum=9.7407 +/- 0.0315 Interval 7, DeltaF=-1.7472 +/- 0.1420, Sum=8.7058 +/- 0.0337 Interval 8, DeltaF=-2.2550 +/- 0.0956, Sum=7.3701 +/- 0.0341 Interval 9, DeltaF=-2.9206 +/- 0.0632, Sum=5.6402 +/- 0.0342 Interval 10, DeltaF=-1.0740 +/- 0.0260, Sum=5.0040 +/- 0.0342 Average EXP free energy: 5.0040 +/- 0.0342 Interval 1, DeltaF=6.4712 +/- 0.1386, Sum=3.8331 +/- 0.0114 Interval 2, DeltaF=1.8503 +/- 0.2728, Sum=4.9291 +/- 0.0455 Interval 3, DeltaF=3.0794 +/- 0.2336, Sum=6.7532 +/- 0.0558 Interval 4, DeltaF=4.1549 +/- 0.3131, Sum=9.2143 +/- 0.0805 Interval 5, DeltaF=0.8209 +/- 0.3494, Sum=9.7005 +/- 0.1082 Interval 6, DeltaF=-0.6630 +/- 0.4822, Sum=9.3078 +/- 0.1751 Interval 7, DeltaF=-1.7373 +/- 0.4289, Sum=8.2787 +/- 0.2063 Interval 8, DeltaF=-2.3227 +/- 0.5603, Sum=6.9029 +/- 0.2777 Interval 9, DeltaF=-3.0414 +/- 0.4751, Sum=5.1014 +/- 0.3082 Interval 10, DeltaF=-1.0974 +/- 0.5778, Sum=4.4514 +/- 0.3662 Double-Wide EXP free energy: 4.4514 +/- 0.3662 Method: BAR Interval 1, DeltaF=6.7459 +/- 0.2976, Sum=3.9959 +/- 0.0525 Interval 2, DeltaF=1.9179 +/- 0.1938, Sum=5.1319 +/- 0.0570 Interval 3, DeltaF=3.1913 +/- 0.2575, Sum=7.0222 +/- 0.0692 Interval 4, DeltaF=3.4322 +/- 0.2985, Sum=9.0552 +/- 0.0870 Interval 5, DeltaF=1.0497 +/- 0.3489, Sum=9.6770 +/- 0.1130 Interval 6, DeltaF=-0.4840 +/- 0.2280, Sum=9.3903 +/- 0.1172 Interval 7, DeltaF=-1.6989 +/- 0.2910, Sum=8.3840 +/- 0.1274 Interval 8, DeltaF=-2.2565 +/- 0.2581, Sum=7.0474 +/- 0.1334 Interval 9, DeltaF=-2.8791 +/- 0.2272, Sum=5.3420 +/- 0.1369 Interval 10, DeltaF=-1.0845 +/- 0.1499, Sum=4.6996 +/- 0.1375 BAR free energy: 4.6996 +/- 0.1375 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9820 +/- 0.4364, Sum=4.1357 +/- 0.1128 Interval 2, DeltaF=1.8813 +/- 0.2544, Sum=5.2500 +/- 0.1191 Interval 3, DeltaF=3.3615 +/- 0.3642, Sum=7.2412 +/- 0.1427 Interval 4, DeltaF=3.5423 +/- 0.3908, Sum=9.3394 +/- 0.1690 Interval 5, DeltaF=1.0379 +/- 0.3772, Sum=9.9542 +/- 0.1888 Interval 6, DeltaF=-0.4773 +/- 0.2279, Sum=9.6715 +/- 0.1913 Interval 7, DeltaF=-1.7093 +/- 0.2256, Sum=8.6590 +/- 0.1937 Interval 8, DeltaF=-2.2100 +/- 0.3766, Sum=7.3500 +/- 0.2111 Interval 9, DeltaF=-2.9815 +/- 0.3914, Sum=5.5839 +/- 0.2298 Interval 10, DeltaF=-1.0705 +/- 0.2356, Sum=4.9498 +/- 0.2321 Unopt. BAR free energy: 4.9498 +/- 0.2321 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7430 +/- 0.2985, Sum=3.9941 +/- 0.0528 Interval 2, DeltaF=1.9192 +/- 0.1942, Sum=5.1309 +/- 0.0573 Interval 3, DeltaF=3.1958 +/- 0.2613, Sum=7.0239 +/- 0.0701 Interval 4, DeltaF=3.4354 +/- 0.3097, Sum=9.0589 +/- 0.0903 Interval 5, DeltaF=1.0498 +/- 0.3504, Sum=9.6807 +/- 0.1159 Interval 6, DeltaF=-0.4773 +/- 0.2279, Sum=9.3979 +/- 0.1199 Interval 7, DeltaF=-1.7021 +/- 0.3043, Sum=8.3897 +/- 0.1319 Interval 8, DeltaF=-2.2495 +/- 0.2644, Sum=7.0573 +/- 0.1382 Interval 9, DeltaF=-2.8755 +/- 0.2241, Sum=5.3540 +/- 0.1414 Interval 10, DeltaF=-1.0835 +/- 0.1551, Sum=4.7122 +/- 0.1421 Postopt. BAR free energy: 4.7122 +/- 0.1421 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 941 N_k = [441 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.41418084] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.74109231] relative max_delta = 2.798746e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9381 relative max_delta = 3.989289e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7096 relative max_delta = 2.640303e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7459 relative max_delta = 5.375854e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7459 relative max_delta = 3.049452e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7459 relative max_delta = 9.778506e-13 Converged to tolerance of 9.778506e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7459 Final dimensionless free energies f_k = [ 0. 6.74591933] Computing normalized weights... Interval 1, DeltaF=6.7459 +/- 0.2976, Sum=3.9959 +/- 0.0525 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 990 N_k = [500 490] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.49260233] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.81006677] relative max_delta = 1.753882e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8208 relative max_delta = 5.919297e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9178 relative max_delta = 5.057678e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9179 relative max_delta = 1.121663e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9179 relative max_delta = 2.376323e-12 Converged to tolerance of 2.376323e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9179 Final dimensionless free energies f_k = [ 0. 1.91786473] Computing normalized weights... Interval 2, DeltaF=1.9179 +/- 0.1938, Sum=5.1319 +/- 0.0570 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 826 N_k = [490 336] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.67385834] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.46972967] relative max_delta = 3.222504e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5468 relative max_delta = 3.027265e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2294 relative max_delta = 2.113705e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1914 relative max_delta = 1.192294e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1913 relative max_delta = 2.959158e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1913 relative max_delta = 1.855521e-10 Converged to tolerance of 1.855521e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1913 Final dimensionless free energies f_k = [ 0. 3.19129159] Computing normalized weights... Interval 3, DeltaF=3.1913 +/- 0.2575, Sum=7.0222 +/- 0.0692 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 709 N_k = [336 373] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.0631404] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.85385324] relative max_delta = 4.265240e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0444 relative max_delta = 9.321190e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6796 relative max_delta = 4.443954e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4375 relative max_delta = 7.044346e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4322 relative max_delta = 1.538264e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4322 relative max_delta = 7.702780e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4322 relative max_delta = 1.925312e-13 Converged to tolerance of 1.925312e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4322 Final dimensionless free energies f_k = [ 0. 3.43219579] Computing normalized weights... Interval 4, DeltaF=3.4322 +/- 0.2985, Sum=9.0552 +/- 0.0870 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 718 N_k = [373 345] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.25692451] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.45568441] relative max_delta = 4.361788e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5194 relative max_delta = 1.226969e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.0844 relative max_delta = 5.210076e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0498 relative max_delta = 3.290968e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0497 relative max_delta = 1.442868e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0497 relative max_delta = 2.749947e-09 Converged to tolerance of 2.749947e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0497 Final dimensionless free energies f_k = [ 0. 1.04968955] Computing normalized weights... Interval 5, DeltaF=1.0497 +/- 0.3489, Sum=9.6770 +/- 0.1130 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 763 N_k = [345 418] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.32986534] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.43281379] relative max_delta = 2.378585e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4379 relative max_delta = 1.166719e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4839 relative max_delta = 9.504731e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4840 relative max_delta = 1.068627e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4840 relative max_delta = 1.530231e-10 Converged to tolerance of 1.530231e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4840 Final dimensionless free energies f_k = [ 0. -0.48396997] Computing normalized weights... Interval 6, DeltaF=-0.4840 +/- 0.2280, Sum=9.3903 +/- 0.1172 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 581 N_k = [418 163] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97519244] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.37528054] relative max_delta = 2.909138e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4063 relative max_delta = 2.206602e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6879 relative max_delta = 1.668425e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6988 relative max_delta = 6.419001e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6989 relative max_delta = 9.618716e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6989 relative max_delta = 2.159262e-11 Converged to tolerance of 2.159262e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6989 Final dimensionless free energies f_k = [ 0. -1.69885196] Computing normalized weights... Interval 7, DeltaF=-1.6989 +/- 0.2910, Sum=8.3840 +/- 0.1274 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 397 N_k = [163 234] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.70045922] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.09507675] relative max_delta = 1.883547e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1114 relative max_delta = 7.716601e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2577 relative max_delta = 6.481351e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2565 relative max_delta = 5.156557e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2565 relative max_delta = 2.744660e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2565 relative max_delta = 9.840069e-16 Converged to tolerance of 9.840069e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2565 Final dimensionless free energies f_k = [ 0. -2.25653508] Computing normalized weights... Interval 8, DeltaF=-2.2565 +/- 0.2581, Sum=7.0474 +/- 0.1334 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 544 N_k = [234 310] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.1898227] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.69585212] relative max_delta = 1.877067e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7144 relative max_delta = 6.846739e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8812 relative max_delta = 5.786609e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8791 relative max_delta = 7.241670e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8791 relative max_delta = 9.736028e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8791 relative max_delta = 4.627418e-16 Converged to tolerance of 4.627418e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8791 Final dimensionless free energies f_k = [ 0. -2.87907335] Computing normalized weights... Interval 9, DeltaF=-2.8791 +/- 0.2272, Sum=5.3420 +/- 0.1369 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 718 N_k = [310 408] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00120334] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.0777329] relative max_delta = 7.100977e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0784 relative max_delta = 6.310566e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0845 relative max_delta = 5.646920e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0845 relative max_delta = 2.193089e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0845 relative max_delta = 3.263509e-13 Converged to tolerance of 3.263509e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0845 Final dimensionless free energies f_k = [ 0. -1.08453536] Computing normalized weights... Interval 10, DeltaF=-1.0845 +/- 0.1499, Sum=4.6996 +/- 0.1375 Pairwise MBAR free energy: 4.6996 +/- 0.1375 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4018 N_k = [441 500 490 336 373 345 418 163 234 310 408] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.09726038 2.19440574 1.93896223 1.63826047 1.66787013 1.66399102 1.66491968 1.59310722 1.01027355 0.57465272] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.12679438 3.61757284 3.51759838 3.02598289 3.03705691 3.00568668 2.91863944 2.65901384 1.6376452 1.0191695 ] relative max_delta = 4.363799e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3856 4.0051 4.4844 4.6491 4.7851 4.7124 4.5165 4.0922 2.8588 2.1883 relative max_delta = 3.653031e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8359 7.6224 12.4107 17.8563 19.0823 18.6336 17.3875 15.3816 12.2540 11.1297 relative max_delta = 7.492415e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7502 8.8368 12.0228 16.1935 17.2834 16.8016 15.1335 12.8625 9.9701 8.8942 relative max_delta = 1.457492e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7484 8.6553 11.8553 15.3294 16.4201 15.9335 14.2502 11.9595 9.0862 8.0090 relative max_delta = 5.499514e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7466 8.6565 11.8357 15.2396 16.3324 15.8457 14.1624 11.8716 8.9984 7.9212 relative max_delta = 5.501481e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7466 8.6564 11.8356 15.2385 16.3314 15.8447 14.1614 11.8706 8.9975 7.9202 relative max_delta = 6.206977e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7466 8.6564 11.8356 15.2385 16.3314 15.8447 14.1614 11.8706 8.9975 7.9202 relative max_delta = 8.039161e-09 Converged to tolerance of 8.039161e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7466 8.6564 11.8356 15.2385 16.3314 15.8447 14.1614 11.8706 8.9975 7.9202 Final dimensionless free energies f_k = [ 0. 6.74662654 8.65643841 11.83557228 15.23854092 16.33143342 15.84473482 14.16139689 11.87063131 8.99745063 7.9202235 ] Computing normalized weights... DeltaMij: [[ 0. 3.99627885 5.12753175 7.01065146 9.02635687 9.67371791 9.38542815 8.38832424 7.03141824 5.32952602 4.69144416] [-3.99627885 0. 1.1312529 3.01437261 5.03007802 5.67743906 5.38914931 4.39204539 3.03513939 1.33324717 0.69516531] [-5.12753175 -1.1312529 0. 1.88311972 3.89882512 4.54618616 4.25789641 3.26079249 1.90388649 0.20199427 -0.43608758] [-7.01065146 -3.01437261 -1.88311972 0. 2.01570541 2.66306645 2.37477669 1.37767278 0.02076677 -1.68112544 -2.3192073 ] [-9.02635687 -5.03007802 -3.89882512 -2.01570541 0. 0.64736104 0.35907128 -0.63803263 -1.99493864 -3.69683085 -4.33491271] [-9.67371791 -5.67743906 -4.54618616 -2.66306645 -0.64736104 0. -0.28828976 -1.28539367 -2.64229968 -4.34419189 -4.98227375] [-9.38542815 -5.38914931 -4.25789641 -2.37477669 -0.35907128 0.28828976 0. -0.99710392 -2.35400992 -4.05590213 -4.69398399] [-8.38832424 -4.39204539 -3.26079249 -1.37767278 0.63803263 1.28539367 0.99710392 0. -1.356906 -3.05879822 -3.69688008] [-7.03141824 -3.03513939 -1.90388649 -0.02076677 1.99493864 2.64229968 2.35400992 1.356906 0. -1.70189221 -2.33997407] [-5.32952602 -1.33324717 -0.20199427 1.68112544 3.69683085 4.34419189 4.05590213 3.05879822 1.70189221 0. -0.63808186] [-4.69144416 -0.69516531 0.43608758 2.3192073 4.33491271 4.98227375 4.69398399 3.69688008 2.33997407 0.63808186 0. ]] dDeltaMij: [[ 0. 0.05127463 0.06339621 0.07660112 0.09687123 0.1241659 0.13255248 0.14430982 0.1550117 0.16161443 0.16380361] [ 0.05127463 0. 0.02151288 0.04722644 0.07581899 0.10854345 0.1180452 0.13111 0.14280454 0.14994577 0.15230276] [ 0.06339621 0.02151288 0. 0.03517988 0.06924215 0.10405681 0.11393334 0.12742044 0.13942479 0.1467306 0.14913842] [ 0.07660112 0.04722644 0.03517988 0. 0.0515427 0.09316329 0.10407973 0.1186918 0.13149543 0.13921798 0.14175346] [ 0.09687123 0.07581899 0.06924215 0.0515427 0. 0.06691867 0.08138163 0.09939082 0.11437565 0.12317626 0.12603487] [ 0.1241659 0.10854345 0.10405681 0.09316329 0.06691867 0. 0.03021824 0.06416868 0.08560375 0.09704698 0.10065028] [ 0.13255248 0.1180452 0.11393334 0.10407973 0.08138163 0.03021824 0. 0.04522046 0.07190955 0.08525232 0.08933401] [ 0.14430982 0.13111 0.12742044 0.1186918 0.09939082 0.06416868 0.04522046 0. 0.03563153 0.05562619 0.06173747] [ 0.1550117 0.14280454 0.13942479 0.13149543 0.11437565 0.08560375 0.07190955 0.03563153 0. 0.02535235 0.03479253] [ 0.16161443 0.14994577 0.1467306 0.13921798 0.12317626 0.09704698 0.08525232 0.05562619 0.02535235 0. 0.0121155 ] [ 0.16380361 0.15230276 0.14913842 0.14175346 0.12603487 0.10065028 0.08933401 0.06173747 0.03479253 0.0121155 0. ]] Replica 22 / 40 Computing statistical inefficiencies: lambda 0: g = 1.337 lambda 1: g = 1.792 lambda 2: g = 1.185 lambda 3: g = 1.542 lambda 4: g = 1.335 lambda 5: g = 1.996 lambda 6: g = 2.236 lambda 7: g = 1.576 lambda 8: g = 2.656 lambda 9: g = 2.157 lambda 10: g = 1.015 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 325 500 373 464 255 208 311 260 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.5992 +/- 0.4772, Sum=3.9090 +/- 0.1349 Interval 2, DeltaF=1.8054 +/- 0.2725, Sum=4.9784 +/- 0.1419 Interval 3, DeltaF=3.3212 +/- 0.4186, Sum=6.9456 +/- 0.1758 Interval 4, DeltaF=3.5012 +/- 0.5316, Sum=9.0195 +/- 0.2427 Interval 5, DeltaF=2.3806 +/- 0.3698, Sum=10.4296 +/- 0.2559 Interval 6, DeltaF=-0.3455 +/- 0.3602, Sum=10.2249 +/- 0.2672 Interval 7, DeltaF=-1.9696 +/- 0.5480, Sum=9.0582 +/- 0.3210 Interval 8, DeltaF=-2.5184 +/- 0.4170, Sum=7.5665 +/- 0.3371 Interval 9, DeltaF=-2.9700 +/- 0.2736, Sum=5.8072 +/- 0.3400 Interval 10, DeltaF=-1.0411 +/- 0.1992, Sum=5.1906 +/- 0.3408 Forward EXP free energy: 5.1906 +/- 0.3408 Reverse EXP: Interval 1, DeltaF=6.5514 +/- 0.5473, Sum=3.8806 +/- 0.1774 Interval 2, DeltaF=1.9504 +/- 0.3508, Sum=5.0359 +/- 0.1918 Interval 3, DeltaF=3.1092 +/- 0.4187, Sum=6.8776 +/- 0.2181 Interval 4, DeltaF=3.5340 +/- 0.3943, Sum=8.9709 +/- 0.2367 Interval 5, DeltaF=1.2659 +/- 0.4988, Sum=9.7207 +/- 0.2789 Interval 6, DeltaF=-0.6199 +/- 0.3136, Sum=9.3535 +/- 0.2849 Interval 7, DeltaF=-1.5651 +/- 0.3718, Sum=8.4265 +/- 0.2964 Interval 8, DeltaF=-2.3895 +/- 0.3178, Sum=7.0111 +/- 0.3024 Interval 9, DeltaF=-2.6704 +/- 0.3810, Sum=5.4294 +/- 0.3144 Interval 10, DeltaF=-1.0889 +/- 0.1793, Sum=4.7844 +/- 0.3150 Reverse EXP free energy: 4.7844 +/- 0.3150 Averge of forward and reverse EXP: Interval 1, DeltaF=6.5753 +/- 0.2047, Sum=3.8948 +/- 0.0248 Interval 2, DeltaF=1.8779 +/- 0.0782, Sum=5.0071 +/- 0.0251 Interval 3, DeltaF=3.2152 +/- 0.1349, Sum=6.9116 +/- 0.0273 Interval 4, DeltaF=3.5176 +/- 0.1755, Sum=8.9952 +/- 0.0328 Interval 5, DeltaF=1.8232 +/- 0.1545, Sum=10.0752 +/- 0.0358 Interval 6, DeltaF=-0.4827 +/- 0.0886, Sum=9.7892 +/- 0.0361 Interval 7, DeltaF=-1.7673 +/- 0.1799, Sum=8.7424 +/- 0.0408 Interval 8, DeltaF=-2.4539 +/- 0.1094, Sum=7.2888 +/- 0.0415 Interval 9, DeltaF=-2.8202 +/- 0.0889, Sum=5.6183 +/- 0.0417 Interval 10, DeltaF=-1.0650 +/- 0.0278, Sum=4.9875 +/- 0.0417 Average EXP free energy: 4.9875 +/- 0.0417 Interval 1, DeltaF=6.5514 +/- 0.2305, Sum=3.8806 +/- 0.0315 Interval 2, DeltaF=1.8054 +/- 0.2544, Sum=4.9500 +/- 0.0496 Interval 3, DeltaF=3.1092 +/- 0.3773, Sum=6.7917 +/- 0.0978 Interval 4, DeltaF=3.5012 +/- 0.3894, Sum=8.8656 +/- 0.1328 Interval 5, DeltaF=1.2659 +/- 0.4753, Sum=9.6154 +/- 0.1885 Interval 6, DeltaF=-0.3455 +/- 0.4807, Sum=9.4107 +/- 0.2330 Interval 7, DeltaF=-1.5651 +/- 0.5342, Sum=8.4837 +/- 0.2878 Interval 8, DeltaF=-2.5184 +/- 0.6048, Sum=6.9920 +/- 0.3603 Interval 9, DeltaF=-2.6704 +/- 0.5668, Sum=5.4102 +/- 0.4074 Interval 10, DeltaF=-1.0411 +/- 0.6255, Sum=4.7935 +/- 0.4688 Double-Wide EXP free energy: 4.7935 +/- 0.4688 Method: BAR Interval 1, DeltaF=6.5472 +/- 0.2907, Sum=3.8781 +/- 0.0500 Interval 2, DeltaF=1.8677 +/- 0.2017, Sum=4.9844 +/- 0.0555 Interval 3, DeltaF=3.1788 +/- 0.2555, Sum=6.8673 +/- 0.0677 Interval 4, DeltaF=3.3356 +/- 0.2916, Sum=8.8431 +/- 0.0844 Interval 5, DeltaF=1.2262 +/- 0.3188, Sum=9.5694 +/- 0.1036 Interval 6, DeltaF=-0.5363 +/- 0.2464, Sum=9.2518 +/- 0.1097 Interval 7, DeltaF=-1.6264 +/- 0.2886, Sum=8.2884 +/- 0.1203 Interval 8, DeltaF=-2.3347 +/- 0.2516, Sum=6.9055 +/- 0.1260 Interval 9, DeltaF=-2.8960 +/- 0.2166, Sum=5.1901 +/- 0.1290 Interval 10, DeltaF=-1.0675 +/- 0.1526, Sum=4.5578 +/- 0.1297 BAR free energy: 4.5578 +/- 0.1297 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.5696 +/- 0.4452, Sum=3.8914 +/- 0.1174 Interval 2, DeltaF=1.8468 +/- 0.2960, Sum=4.9854 +/- 0.1284 Interval 3, DeltaF=3.2042 +/- 0.3037, Sum=6.8833 +/- 0.1395 Interval 4, DeltaF=3.2322 +/- 0.3944, Sum=8.7979 +/- 0.1672 Interval 5, DeltaF=1.3131 +/- 0.3423, Sum=9.5757 +/- 0.1811 Interval 6, DeltaF=-0.5453 +/- 0.2257, Sum=9.2527 +/- 0.1835 Interval 7, DeltaF=-1.5768 +/- 0.2796, Sum=8.3187 +/- 0.1893 Interval 8, DeltaF=-2.3577 +/- 0.3575, Sum=6.9221 +/- 0.2039 Interval 9, DeltaF=-2.7779 +/- 0.3447, Sum=5.2767 +/- 0.2157 Interval 10, DeltaF=-1.0759 +/- 0.2591, Sum=4.6394 +/- 0.2193 Unopt. BAR free energy: 4.6394 +/- 0.2193 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.5407 +/- 0.2923, Sum=3.8743 +/- 0.0506 Interval 2, DeltaF=1.8686 +/- 0.1990, Sum=4.9811 +/- 0.0558 Interval 3, DeltaF=3.1838 +/- 0.2543, Sum=6.8670 +/- 0.0677 Interval 4, DeltaF=3.3304 +/- 0.3022, Sum=8.8397 +/- 0.0866 Interval 5, DeltaF=1.2431 +/- 0.3231, Sum=9.5760 +/- 0.1064 Interval 6, DeltaF=-0.5281 +/- 0.2672, Sum=9.2632 +/- 0.1145 Interval 7, DeltaF=-1.6437 +/- 0.2987, Sum=8.2896 +/- 0.1261 Interval 8, DeltaF=-2.3350 +/- 0.2600, Sum=6.9065 +/- 0.1323 Interval 9, DeltaF=-2.8992 +/- 0.2176, Sum=5.1892 +/- 0.1353 Interval 10, DeltaF=-1.0681 +/- 0.1608, Sum=4.5565 +/- 0.1361 Postopt. BAR free energy: 4.5565 +/- 0.1361 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.42222082] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.71028138] relative max_delta = 2.734572e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.8925 relative max_delta = 3.725390e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5277 relative max_delta = 2.504898e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5472 relative max_delta = 2.977860e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5472 relative max_delta = 9.387431e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5472 relative max_delta = 9.374004e-14 Converged to tolerance of 9.374004e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5472 Final dimensionless free energies f_k = [ 0. 6.54716264] Computing normalized weights... Interval 1, DeltaF=6.5472 +/- 0.2907, Sum=3.8781 +/- 0.0500 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 825 N_k = [500 325] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.49362392] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.77834541] relative max_delta = 1.601047e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7873 relative max_delta = 5.026840e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.8681 relative max_delta = 4.323010e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.8677 relative max_delta = 2.221143e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.8677 relative max_delta = 5.304196e-09 Converged to tolerance of 5.304196e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.8677 Final dimensionless free energies f_k = [ 0. 1.86767281] Computing normalized weights... Interval 2, DeltaF=1.8677 +/- 0.2017, Sum=4.9844 +/- 0.0555 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 825 N_k = [325 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.63960346] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.4485136] relative max_delta = 3.303678e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5215 relative max_delta = 2.895666e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1775 relative max_delta = 2.064331e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1788 relative max_delta = 4.084778e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1788 relative max_delta = 1.532891e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1788 relative max_delta = 2.794103e-16 Converged to tolerance of 2.794103e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1788 Final dimensionless free energies f_k = [ 0. 3.17876062] Computing normalized weights... Interval 3, DeltaF=3.1788 +/- 0.2555, Sum=6.8673 +/- 0.0677 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 873 N_k = [500 373] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.98852957] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.73449693] relative max_delta = 4.300771e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9371 relative max_delta = 1.045786e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6532 relative max_delta = 4.697649e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3477 relative max_delta = 9.126777e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 3.633348e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 5.720311e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3356 relative max_delta = 1.417226e-11 Converged to tolerance of 1.417226e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3356 Final dimensionless free energies f_k = [ 0. 3.33555952] Computing normalized weights... Interval 4, DeltaF=3.3356 +/- 0.2916, Sum=8.8431 +/- 0.0844 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 837 N_k = [373 464] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.35089841] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.60863356] relative max_delta = 4.234652e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6737 relative max_delta = 9.652510e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2523 relative max_delta = 4.620508e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2263 relative max_delta = 2.118681e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2262 relative max_delta = 4.526298e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2262 relative max_delta = 2.061593e-10 Converged to tolerance of 2.061593e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2262 Final dimensionless free energies f_k = [ 0. 1.22623502] Computing normalized weights... Interval 5, DeltaF=1.2262 +/- 0.3188, Sum=9.5694 +/- 0.1036 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 719 N_k = [464 255] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.34155403] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.46375117] relative max_delta = 2.634972e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4709 relative max_delta = 1.525675e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5357 relative max_delta = 1.209351e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5363 relative max_delta = 1.007719e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5363 relative max_delta = 7.100818e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5363 relative max_delta = 3.105436e-15 Converged to tolerance of 3.105436e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5363 Final dimensionless free energies f_k = [ 0. -0.53626439] Computing normalized weights... Interval 6, DeltaF=-0.5363 +/- 0.2464, Sum=9.2518 +/- 0.1097 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 463 N_k = [255 208] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99608971] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35912763] relative max_delta = 2.671110e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3854 relative max_delta = 1.895948e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6226 relative max_delta = 1.461869e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6264 relative max_delta = 2.363074e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6264 relative max_delta = 6.879850e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6264 relative max_delta = 5.638350e-14 Converged to tolerance of 5.638350e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6264 Final dimensionless free energies f_k = [ 0. -1.62644088] Computing normalized weights... Interval 7, DeltaF=-1.6264 +/- 0.2886, Sum=8.2884 +/- 0.1203 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 519 N_k = [208 311] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.68241729] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.12250421] relative max_delta = 2.073433e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1440 relative max_delta = 1.003448e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3370 relative max_delta = 8.258726e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3347 relative max_delta = 1.016174e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3347 relative max_delta = 1.326651e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3347 relative max_delta = 3.804325e-15 Converged to tolerance of 3.804325e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3347 Final dimensionless free energies f_k = [ 0. -2.33465424] Computing normalized weights... Interval 8, DeltaF=-2.3347 +/- 0.2516, Sum=6.9055 +/- 0.1260 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 571 N_k = [311 260] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.20259686] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.72551968] relative max_delta = 1.918617e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7426 relative max_delta = 6.217387e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8960 relative max_delta = 5.297949e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8960 relative max_delta = 8.380124e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8960 relative max_delta = 2.859874e-12 Converged to tolerance of 2.859874e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8960 Final dimensionless free energies f_k = [ 0. -2.89602418] Computing normalized weights... Interval 9, DeltaF=-2.8960 +/- 0.2166, Sum=5.1901 +/- 0.1290 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 760 N_k = [260 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98550757] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06055717] relative max_delta = 7.076431e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0613 relative max_delta = 6.532460e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0675 relative max_delta = 5.843655e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0675 relative max_delta = 5.104626e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0675 relative max_delta = 3.881422e-12 Converged to tolerance of 3.881422e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0675 Final dimensionless free energies f_k = [ 0. -1.06748301] Computing normalized weights... Interval 10, DeltaF=-1.0675 +/- 0.1526, Sum=4.5578 +/- 0.1297 Pairwise MBAR free energy: 4.5578 +/- 0.1297 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4196 N_k = [500 500 325 500 373 464 255 208 311 260 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.94083003 1.90179678 1.80888194 1.47178304 1.55697713 1.62053037 1.65291465 1.58073531 0.9189938 0.47276851] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.88838097 3.18972755 3.2845285 2.7595261 2.87662296 2.94226593 2.91312599 2.6405409 1.48142055 0.84458329] relative max_delta = 4.492720e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1619 3.5986 4.1709 4.3267 4.5676 4.5851 4.4479 3.9984 2.6218 1.9337 relative max_delta = 3.687921e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7567 7.4345 11.6873 17.2179 18.5433 18.1156 16.9399 14.8116 11.5471 10.4172 relative max_delta = 7.536799e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5620 8.5755 11.7307 15.7163 16.9145 16.4054 14.8181 12.5266 9.5989 8.5136 relative max_delta = 1.350899e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.5586 8.4217 11.6159 15.0277 16.2294 15.7118 14.1101 11.8033 8.8937 7.8085 relative max_delta = 4.456808e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.5576 8.4212 11.6067 14.9670 16.1709 15.6531 14.0514 11.7446 8.8350 7.7499 relative max_delta = 3.753012e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.5576 8.4212 11.6067 14.9666 16.1704 15.6527 14.0510 11.7441 8.8346 7.7494 relative max_delta = 2.981428e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.5576 8.4212 11.6067 14.9666 16.1704 15.6527 14.0510 11.7441 8.8346 7.7494 relative max_delta = 1.964251e-09 Converged to tolerance of 1.964251e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.5576 8.4212 11.6067 14.9666 16.1704 15.6527 14.0510 11.7441 8.8346 7.7494 Final dimensionless free energies f_k = [ 0. 6.5576439 8.42115816 11.60668161 14.96656752 16.17039988 15.65268723 14.05097824 11.74410621 8.83457115 7.74939065] Computing normalized weights... DeltaMij: [[ 0. 3.88433738 4.98816646 6.87507097 8.86525687 9.57833173 9.2716712 8.32291914 6.95647269 5.23304642 4.59025348] [-3.88433738 0. 1.10382909 2.99073359 4.98091949 5.69399435 5.38733382 4.43858177 3.07213532 1.34870904 0.70591611] [-4.98816646 -1.10382909 0. 1.8869045 3.8770904 4.59016527 4.28350473 3.33475268 1.96830623 0.24487996 -0.39791298] [-6.87507097 -2.99073359 -1.8869045 0. 1.9901859 2.70326076 2.39660023 1.44784818 0.08140173 -1.64202455 -2.28481748] [-8.86525687 -4.98091949 -3.8770904 -1.9901859 0. 0.71307486 0.40641433 -0.54233772 -1.90878417 -3.63221045 -4.27500338] [-9.57833173 -5.69399435 -4.59016527 -2.70326076 -0.71307486 0. -0.30666053 -1.25541259 -2.62185904 -4.34528531 -4.98807825] [-9.2716712 -5.38733382 -4.28350473 -2.39660023 -0.40641433 0.30666053 0. -0.94875205 -2.3151985 -4.03862478 -4.68141771] [-8.32291914 -4.43858177 -3.33475268 -1.44784818 0.54233772 1.25541259 0.94875205 0. -1.36644645 -3.08987272 -3.73266566] [-6.95647269 -3.07213532 -1.96830623 -0.08140173 1.90878417 2.62185904 2.3151985 1.36644645 0. -1.72342627 -2.36621921] [-5.23304642 -1.34870904 -0.24487996 1.64202455 3.63221045 4.34528531 4.03862478 3.08987272 1.72342627 0. -0.64279294] [-4.59025348 -0.70591611 0.39791298 2.28481748 4.27500338 4.98807825 4.68141771 3.73266566 2.36621921 0.64279294 0. ]] dDeltaMij: [[ 0. 0.04912797 0.06205361 0.0754593 0.09369586 0.11737876 0.12644838 0.13984145 0.15024856 0.15568579 0.1576625 ] [ 0.04912797 0. 0.02250731 0.04741669 0.07307082 0.10167738 0.11202547 0.12694938 0.13832983 0.14421712 0.14634882] [ 0.06205361 0.02250731 0. 0.03407456 0.06554702 0.09641261 0.10726978 0.12277314 0.13450741 0.1405549 0.1427413 ] [ 0.0754593 0.04741669 0.03407456 0. 0.04904927 0.085996 0.09801459 0.11477492 0.1272489 0.13362529 0.1359232 ] [ 0.09369586 0.07307082 0.06554702 0.04904927 0. 0.05918516 0.07554759 0.09630518 0.11087669 0.11814008 0.12073309] [ 0.11737876 0.10167738 0.09641261 0.085996 0.05918516 0. 0.03380058 0.06815902 0.08757292 0.09660297 0.09975726] [ 0.12644838 0.11202547 0.10726978 0.09801459 0.07554759 0.03380058 0. 0.04524223 0.07040906 0.08142782 0.08514727] [ 0.13984145 0.12694938 0.12277314 0.11477492 0.09630518 0.06815902 0.04524223 0. 0.0341216 0.05145693 0.05722436] [ 0.15024856 0.13832983 0.13450741 0.1272489 0.11087669 0.08757292 0.07040906 0.0341216 0. 0.02272487 0.03189195] [ 0.15568579 0.14421712 0.1405549 0.13362529 0.11814008 0.09660297 0.08142782 0.05145693 0.02272487 0. 0.01170402] [ 0.1576625 0.14634882 0.1427413 0.1359232 0.12073309 0.09975726 0.08514727 0.05722436 0.03189195 0.01170402 0. ]] Replica 23 / 40 Computing statistical inefficiencies: lambda 0: g = 1.312 lambda 1: g = 1.253 lambda 2: g = 1.636 lambda 3: g = 1.909 lambda 4: g = 1.850 lambda 5: g = 3.168 lambda 6: g = 2.029 lambda 7: g = 2.396 lambda 8: g = 1.911 lambda 9: g = 2.743 lambda 10: g = 1.533 Subsampling data to produce uncorrelated samples... number of samples per lambda: [486 481 442 481 331 500 325 210 207 360 431] Method: EXP Forward EXP: Interval 1, DeltaF=6.3427 +/- 0.5256, Sum=3.7570 +/- 0.1636 Interval 2, DeltaF=2.0122 +/- 0.2478, Sum=4.9489 +/- 0.1676 Interval 3, DeltaF=3.6395 +/- 0.3429, Sum=7.1047 +/- 0.1815 Interval 4, DeltaF=3.8967 +/- 0.5074, Sum=9.4129 +/- 0.2371 Interval 5, DeltaF=1.9574 +/- 0.4286, Sum=10.5723 +/- 0.2609 Interval 6, DeltaF=-0.5855 +/- 0.3483, Sum=10.2255 +/- 0.2706 Interval 7, DeltaF=-1.7646 +/- 0.4432, Sum=9.1802 +/- 0.2945 Interval 8, DeltaF=-2.3406 +/- 0.3347, Sum=7.7938 +/- 0.3019 Interval 9, DeltaF=-2.8970 +/- 0.2946, Sum=6.0777 +/- 0.3063 Interval 10, DeltaF=-1.1551 +/- 0.1711, Sum=5.3935 +/- 0.3067 Forward EXP free energy: 5.3935 +/- 0.3067 Reverse EXP: Interval 1, DeltaF=6.3597 +/- 0.4854, Sum=3.7671 +/- 0.1396 Interval 2, DeltaF=2.0028 +/- 0.2972, Sum=4.9534 +/- 0.1491 Interval 3, DeltaF=3.3888 +/- 0.3850, Sum=6.9607 +/- 0.1730 Interval 4, DeltaF=3.2786 +/- 0.3907, Sum=8.9028 +/- 0.1952 Interval 5, DeltaF=0.9602 +/- 0.3956, Sum=9.4715 +/- 0.2161 Interval 6, DeltaF=-0.5233 +/- 0.3081, Sum=9.1615 +/- 0.2233 Interval 7, DeltaF=-2.0772 +/- 0.3860, Sum=7.9311 +/- 0.2401 Interval 8, DeltaF=-2.5562 +/- 0.3268, Sum=6.4169 +/- 0.2483 Interval 9, DeltaF=-3.0461 +/- 0.2877, Sum=4.6126 +/- 0.2531 Interval 10, DeltaF=-1.0901 +/- 0.1830, Sum=3.9669 +/- 0.2539 Reverse EXP free energy: 3.9669 +/- 0.2539 Averge of forward and reverse EXP: Interval 1, DeltaF=6.3512 +/- 0.1976, Sum=3.7620 +/- 0.0231 Interval 2, DeltaF=2.0075 +/- 0.0585, Sum=4.9511 +/- 0.0232 Interval 3, DeltaF=3.5142 +/- 0.1030, Sum=7.0327 +/- 0.0241 Interval 4, DeltaF=3.5877 +/- 0.1629, Sum=9.1578 +/- 0.0287 Interval 5, DeltaF=1.4588 +/- 0.1313, Sum=10.0219 +/- 0.0305 Interval 6, DeltaF=-0.5544 +/- 0.0838, Sum=9.6935 +/- 0.0308 Interval 7, DeltaF=-1.9209 +/- 0.1342, Sum=8.5556 +/- 0.0326 Interval 8, DeltaF=-2.4484 +/- 0.0842, Sum=7.1053 +/- 0.0328 Interval 9, DeltaF=-2.9716 +/- 0.0653, Sum=5.3452 +/- 0.0329 Interval 10, DeltaF=-1.1226 +/- 0.0242, Sum=4.6802 +/- 0.0329 Average EXP free energy: 4.6802 +/- 0.0329 Interval 1, DeltaF=6.3597 +/- 0.1814, Sum=3.7671 +/- 0.0195 Interval 2, DeltaF=2.0122 +/- 0.3044, Sum=4.9589 +/- 0.0582 Interval 3, DeltaF=3.3888 +/- 0.2967, Sum=6.9662 +/- 0.0782 Interval 4, DeltaF=3.8967 +/- 0.3880, Sum=9.2744 +/- 0.1186 Interval 5, DeltaF=0.9602 +/- 0.3784, Sum=9.8431 +/- 0.1458 Interval 6, DeltaF=-0.5855 +/- 0.4883, Sum=9.4963 +/- 0.2030 Interval 7, DeltaF=-2.0772 +/- 0.4260, Sum=8.2659 +/- 0.2297 Interval 8, DeltaF=-2.3406 +/- 0.5480, Sum=6.8794 +/- 0.2905 Interval 9, DeltaF=-3.0461 +/- 0.4607, Sum=5.0751 +/- 0.3166 Interval 10, DeltaF=-1.1551 +/- 0.5632, Sum=4.3909 +/- 0.3681 Double-Wide EXP free energy: 4.3909 +/- 0.3681 Method: BAR Interval 1, DeltaF=6.7482 +/- 0.2940, Sum=3.9972 +/- 0.0512 Interval 2, DeltaF=1.9889 +/- 0.1948, Sum=5.1753 +/- 0.0559 Interval 3, DeltaF=3.3612 +/- 0.2439, Sum=7.1662 +/- 0.0661 Interval 4, DeltaF=3.4634 +/- 0.3005, Sum=9.2177 +/- 0.0850 Interval 5, DeltaF=1.1240 +/- 0.3208, Sum=9.8836 +/- 0.1046 Interval 6, DeltaF=-0.5938 +/- 0.2373, Sum=9.5318 +/- 0.1098 Interval 7, DeltaF=-1.7926 +/- 0.2831, Sum=8.4700 +/- 0.1196 Interval 8, DeltaF=-2.3994 +/- 0.2532, Sum=7.0487 +/- 0.1255 Interval 9, DeltaF=-3.0186 +/- 0.2235, Sum=5.2607 +/- 0.1290 Interval 10, DeltaF=-1.1202 +/- 0.1437, Sum=4.5972 +/- 0.1295 BAR free energy: 4.5972 +/- 0.1295 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.3540 +/- 0.4673, Sum=3.7637 +/- 0.1293 Interval 2, DeltaF=2.0009 +/- 0.2689, Sum=4.9489 +/- 0.1362 Interval 3, DeltaF=3.4623 +/- 0.3300, Sum=6.9998 +/- 0.1507 Interval 4, DeltaF=3.4498 +/- 0.4208, Sum=9.0432 +/- 0.1836 Interval 5, DeltaF=1.1013 +/- 0.3441, Sum=9.6955 +/- 0.1966 Interval 6, DeltaF=-0.5834 +/- 0.2204, Sum=9.3499 +/- 0.1987 Interval 7, DeltaF=-1.9078 +/- 0.2637, Sum=8.2199 +/- 0.2029 Interval 8, DeltaF=-2.4973 +/- 0.3440, Sum=6.7406 +/- 0.2147 Interval 9, DeltaF=-3.0375 +/- 0.4342, Sum=4.9414 +/- 0.2420 Interval 10, DeltaF=-1.1031 +/- 0.2258, Sum=4.2880 +/- 0.2439 Unopt. BAR free energy: 4.2880 +/- 0.2439 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7379 +/- 0.2948, Sum=3.9911 +/- 0.0515 Interval 2, DeltaF=1.9888 +/- 0.1947, Sum=5.1692 +/- 0.0562 Interval 3, DeltaF=3.3700 +/- 0.2460, Sum=7.1653 +/- 0.0666 Interval 4, DeltaF=3.4747 +/- 0.3181, Sum=9.2236 +/- 0.0896 Interval 5, DeltaF=1.1224 +/- 0.3234, Sum=9.8884 +/- 0.1090 Interval 6, DeltaF=-0.6014 +/- 0.2519, Sum=9.5322 +/- 0.1153 Interval 7, DeltaF=-1.7847 +/- 0.2889, Sum=8.4751 +/- 0.1254 Interval 8, DeltaF=-2.4120 +/- 0.2551, Sum=7.0463 +/- 0.1312 Interval 9, DeltaF=-3.0190 +/- 0.2244, Sum=5.2581 +/- 0.1346 Interval 10, DeltaF=-1.1180 +/- 0.1496, Sum=4.5958 +/- 0.1352 Postopt. BAR free energy: 4.5958 +/- 0.1352 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 967 N_k = [486 481] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.64147205] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.91422788] relative max_delta = 2.589941e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0960 relative max_delta = 3.567581e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7294 relative max_delta = 2.427236e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7482 relative max_delta = 2.775505e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7482 relative max_delta = 7.335580e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7482 relative max_delta = 5.304202e-14 Converged to tolerance of 5.304202e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7482 Final dimensionless free energies f_k = [ 0. 6.74815699] Computing normalized weights... Interval 1, DeltaF=6.7482 +/- 0.2940, Sum=3.9972 +/- 0.0512 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 923 N_k = [481 442] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.56626639] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.88571856] relative max_delta = 1.694061e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8960 relative max_delta = 5.447163e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9890 relative max_delta = 4.671839e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9889 relative max_delta = 4.786004e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9889 relative max_delta = 1.611059e-11 Converged to tolerance of 1.611059e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9889 Final dimensionless free energies f_k = [ 0. 1.98887284] Computing normalized weights... Interval 2, DeltaF=1.9889 +/- 0.1948, Sum=5.1753 +/- 0.0559 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 923 N_k = [442 481] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.76701064] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.62220149] relative max_delta = 3.261347e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6984 relative max_delta = 2.824290e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3783 relative max_delta = 2.012483e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3612 relative max_delta = 5.081097e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3612 relative max_delta = 7.627260e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3612 relative max_delta = 1.796859e-14 Converged to tolerance of 1.796859e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3612 Final dimensionless free energies f_k = [ 0. 3.36120597] Computing normalized weights... Interval 3, DeltaF=3.3612 +/- 0.2439, Sum=7.1662 +/- 0.0661 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 812 N_k = [481 331] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.93696138] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.6757389] relative max_delta = 4.408667e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9194 relative max_delta = 1.269595e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.9384 relative max_delta = 5.126423e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4932 relative max_delta = 1.274535e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4636 relative max_delta = 8.565334e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4634 relative max_delta = 3.846450e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4634 relative max_delta = 7.747416e-10 Converged to tolerance of 7.747416e-10 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4634 Final dimensionless free energies f_k = [ 0. 3.46341689] Computing normalized weights... Interval 4, DeltaF=3.4634 +/- 0.3005, Sum=9.2177 +/- 0.0850 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 831 N_k = [331 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.31964121] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.55587294] relative max_delta = 4.249743e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6157 relative max_delta = 9.716473e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.1480 relative max_delta = 4.636882e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.1241 relative max_delta = 2.129887e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.1240 relative max_delta = 4.430960e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.1240 relative max_delta = 1.918613e-10 Converged to tolerance of 1.918613e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.1240 Final dimensionless free energies f_k = [ 0. 1.12402906] Computing normalized weights... Interval 5, DeltaF=1.1240 +/- 0.3208, Sum=9.8836 +/- 0.1046 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 825 N_k = [500 325] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.37597106] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.51138591] relative max_delta = 2.647997e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5196 relative max_delta = 1.572617e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5932 relative max_delta = 1.241817e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5938 relative max_delta = 9.775389e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5938 relative max_delta = 6.195161e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5938 relative max_delta = 2.430581e-15 Converged to tolerance of 2.430581e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5938 Final dimensionless free energies f_k = [ 0. -0.59380461] Computing normalized weights... Interval 6, DeltaF=-0.5938 +/- 0.2373, Sum=9.5318 +/- 0.1098 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 535 N_k = [325 210] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.06072209] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.47278733] relative max_delta = 2.797860e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.5040 relative max_delta = 2.075856e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7863 relative max_delta = 1.580419e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7926 relative max_delta = 3.518595e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7926 relative max_delta = 1.907784e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7926 relative max_delta = 5.609848e-13 Converged to tolerance of 5.609848e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7926 Final dimensionless free energies f_k = [ 0. -1.79263317] Computing normalized weights... Interval 7, DeltaF=-1.7926 +/- 0.2831, Sum=8.4700 +/- 0.1196 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 417 N_k = [210 207] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.78908416] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.21909873] relative max_delta = 1.937789e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2371 relative max_delta = 8.065293e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3995 relative max_delta = 6.765388e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3994 relative max_delta = 3.584167e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3994 relative max_delta = 1.938332e-11 Converged to tolerance of 1.938332e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3994 Final dimensionless free energies f_k = [ 0. -2.39938979] Computing normalized weights... Interval 8, DeltaF=-2.3994 +/- 0.2532, Sum=7.0487 +/- 0.1255 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 567 N_k = [207 360] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.43031382] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.87422816] relative max_delta = 1.544464e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8889 relative max_delta = 5.079783e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -3.0205 relative max_delta = 4.356711e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -3.0186 relative max_delta = 6.335047e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -3.0186 relative max_delta = 1.257876e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -3.0186 relative max_delta = 4.707787e-15 Converged to tolerance of 4.707787e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -3.0186 Final dimensionless free energies f_k = [ 0. -3.01858485] Computing normalized weights... Interval 9, DeltaF=-3.0186 +/- 0.2235, Sum=5.2607 +/- 0.1290 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 791 N_k = [360 431] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.03620437] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.11365659] relative max_delta = 6.954767e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.1143 relative max_delta = 5.831026e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.1202 relative max_delta = 5.220208e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.1202 relative max_delta = 1.352207e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.1202 relative max_delta = 9.395967e-14 Converged to tolerance of 9.395967e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.1202 Final dimensionless free energies f_k = [ 0. -1.12015227] Computing normalized weights... Interval 10, DeltaF=-1.1202 +/- 0.1437, Sum=4.5972 +/- 0.1295 Pairwise MBAR free energy: 4.5972 +/- 0.1295 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4254 N_k = [486 481 442 481 331 500 325 210 207 360 431] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.03444958 2.05468815 2.00425568 1.50623033 1.61612946 1.63681419 1.63626589 1.57230921 0.99109813 0.51546745] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.0172971 3.43012026 3.6316688 2.82890072 2.95864564 2.96206086 2.87652549 2.62857639 1.60031962 0.94011369] relative max_delta = 4.481172e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2810 3.8363 4.5934 4.5070 4.7494 4.7011 4.4951 4.0738 2.8194 2.1070 relative max_delta = 3.770520e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8013 7.6479 12.5128 18.4136 19.6542 19.1261 17.7565 15.6620 12.3799 11.2125 relative max_delta = 7.583507e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7883 8.9997 12.2372 16.6926 17.8301 17.2181 15.3939 13.0169 10.0042 8.8926 relative max_delta = 1.483536e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7578 8.7312 12.1195 15.7088 16.8537 16.2333 14.3927 11.9888 9.0034 7.8902 relative max_delta = 6.099791e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7557 8.7306 12.0932 15.5611 16.7108 16.0903 14.2498 11.8456 8.8604 7.7472 relative max_delta = 8.839258e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7557 8.7305 12.0928 15.5579 16.7077 16.0872 14.2467 11.8426 8.8573 7.7442 relative max_delta = 1.913347e-04 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7557 8.7305 12.0928 15.5579 16.7077 16.0872 14.2467 11.8426 8.8573 7.7442 relative max_delta = 9.674527e-08 Newton-Raphson iteration 7 current f_k for states with samples = 0.0000 6.7557 8.7305 12.0928 15.5579 16.7077 16.0872 14.2467 11.8426 8.8573 7.7442 relative max_delta = 1.860591e-14 Converged to tolerance of 1.860591e-14 in 8 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7557 8.7305 12.0928 15.5579 16.7077 16.0872 14.2467 11.8426 8.8573 7.7442 Final dimensionless free energies f_k = [ 0. 6.75569362 8.7305085 12.09283779 15.55788967 16.70772401 16.08722522 14.24667629 11.84255547 8.85728918 7.74415234] Computing normalized weights... DeltaMij: [[ 0. 4.00164962 5.17140623 7.16303943 9.21551906 9.89660888 9.52906428 8.43883841 7.01478787 5.24650316 4.58715063] [-4.00164962 0. 1.16975661 3.16138981 5.21386944 5.89495926 5.52741466 4.43718879 3.01313825 1.24485354 0.58550101] [-5.17140623 -1.16975661 0. 1.9916332 4.04411283 4.72520265 4.35765805 3.26743218 1.84338164 0.07509693 -0.58425559] [-7.16303943 -3.16138981 -1.9916332 0. 2.05247963 2.73356945 2.36602485 1.27579898 -0.14825156 -1.91653627 -2.57588879] [-9.21551906 -5.21386944 -4.04411283 -2.05247963 0. 0.68108982 0.31354522 -0.77668065 -2.20073119 -3.9690159 -4.62836843] [-9.89660888 -5.89495926 -4.72520265 -2.73356945 -0.68108982 0. -0.3675446 -1.45777047 -2.88182101 -4.65010572 -5.30945825] [-9.52906428 -5.52741466 -4.35765805 -2.36602485 -0.31354522 0.3675446 0. -1.09022587 -2.51427641 -4.28256112 -4.94191364] [-8.43883841 -4.43718879 -3.26743218 -1.27579898 0.77668065 1.45777047 1.09022587 0. -1.42405054 -3.19233525 -3.85168777] [-7.01478787 -3.01313825 -1.84338164 0.14825156 2.20073119 2.88182101 2.51427641 1.42405054 0. -1.76828471 -2.42763723] [-5.24650316 -1.24485354 -0.07509693 1.91653627 3.9690159 4.65010572 4.28256112 3.19233525 1.76828471 0. -0.65935252] [-4.58715063 -0.58550101 0.58425559 2.57588879 4.62836843 5.30945825 4.94191364 3.85168777 2.42763723 0.65935252 0. ]] dDeltaMij: [[ 0. 0.05002275 0.06243561 0.0743839 0.09477003 0.11888972 0.12737041 0.14019753 0.15074849 0.15715612 0.15917431] [ 0.05002275 0. 0.02152131 0.04475982 0.07384993 0.10299142 0.11267514 0.12699532 0.13855531 0.1455009 0.14767845] [ 0.06243561 0.02152131 0. 0.03170607 0.06700131 0.09819671 0.10830997 0.12313884 0.13502939 0.14214736 0.14437551] [ 0.0743839 0.04475982 0.03170607 0. 0.05247795 0.08886305 0.09992608 0.11583323 0.1284021 0.13586772 0.13819714] [ 0.09477003 0.07384993 0.06700131 0.05247795 0. 0.05893568 0.07453224 0.09480388 0.10980659 0.11845011 0.121115 ] [ 0.11888972 0.10299142 0.09819671 0.08886305 0.05893568 0. 0.03299155 0.06692177 0.08690331 0.09759476 0.10081234] [ 0.12737041 0.11267514 0.10830997 0.09992608 0.07453224 0.03299155 0. 0.04518365 0.07091212 0.08373156 0.08746255] [ 0.14019753 0.12699532 0.12313884 0.11583323 0.09480388 0.06692177 0.04518365 0. 0.03522613 0.05458631 0.06017366] [ 0.15074849 0.13855531 0.13502939 0.1284021 0.10980659 0.08690331 0.07091212 0.03522613 0. 0.02432578 0.03293826] [ 0.15715612 0.1455009 0.14214736 0.13586772 0.11845011 0.09759476 0.08373156 0.05458631 0.02432578 0. 0.01111892] [ 0.15917431 0.14767845 0.14437551 0.13819714 0.121115 0.10081234 0.08746255 0.06017366 0.03293826 0.01111892 0. ]] Replica 24 / 40 Computing statistical inefficiencies: lambda 0: g = 1.495 lambda 1: g = 1.800 lambda 2: g = 1.290 lambda 3: g = 1.970 lambda 4: g = 2.090 lambda 5: g = 1.211 lambda 6: g = 2.425 lambda 7: g = 2.091 lambda 8: g = 2.237 lambda 9: g = 1.676 lambda 10: g = 2.539 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 382 500 500 468 356 299 260 462 441] Method: EXP Forward EXP: Interval 1, DeltaF=6.7117 +/- 0.4229, Sum=3.9756 +/- 0.1059 Interval 2, DeltaF=2.0890 +/- 0.2604, Sum=5.2130 +/- 0.1133 Interval 3, DeltaF=3.4918 +/- 0.4048, Sum=7.2813 +/- 0.1492 Interval 4, DeltaF=4.1078 +/- 0.4344, Sum=9.7145 +/- 0.1864 Interval 5, DeltaF=1.9269 +/- 0.4861, Sum=10.8559 +/- 0.2331 Interval 6, DeltaF=-0.4611 +/- 0.3687, Sum=10.5827 +/- 0.2466 Interval 7, DeltaF=-1.7536 +/- 0.4382, Sum=9.5440 +/- 0.2716 Interval 8, DeltaF=-2.4321 +/- 0.3299, Sum=8.1033 +/- 0.2791 Interval 9, DeltaF=-3.0317 +/- 0.2800, Sum=6.3076 +/- 0.2830 Interval 10, DeltaF=-1.0728 +/- 0.1594, Sum=5.6721 +/- 0.2834 Forward EXP free energy: 5.6721 +/- 0.2834 Reverse EXP: Interval 1, DeltaF=6.8187 +/- 0.4234, Sum=4.0390 +/- 0.1062 Interval 2, DeltaF=1.9651 +/- 0.2823, Sum=5.2030 +/- 0.1162 Interval 3, DeltaF=3.4568 +/- 0.3958, Sum=7.2505 +/- 0.1487 Interval 4, DeltaF=3.5581 +/- 0.3621, Sum=9.3581 +/- 0.1678 Interval 5, DeltaF=1.3851 +/- 0.4423, Sum=10.1786 +/- 0.2039 Interval 6, DeltaF=-0.6408 +/- 0.3048, Sum=9.7990 +/- 0.2112 Interval 7, DeltaF=-1.5363 +/- 0.3514, Sum=8.8890 +/- 0.2235 Interval 8, DeltaF=-2.4486 +/- 0.3536, Sum=7.4386 +/- 0.2354 Interval 9, DeltaF=-3.0350 +/- 0.2585, Sum=5.6409 +/- 0.2387 Interval 10, DeltaF=-1.0535 +/- 0.1883, Sum=5.0168 +/- 0.2397 Reverse EXP free energy: 5.0168 +/- 0.2397 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7652 +/- 0.1378, Sum=4.0073 +/- 0.0112 Interval 2, DeltaF=2.0270 +/- 0.0569, Sum=5.2080 +/- 0.0114 Interval 3, DeltaF=3.4743 +/- 0.1234, Sum=7.2659 +/- 0.0145 Interval 4, DeltaF=3.8330 +/- 0.1251, Sum=9.5363 +/- 0.0172 Interval 5, DeltaF=1.6560 +/- 0.1669, Sum=10.5172 +/- 0.0239 Interval 6, DeltaF=-0.5510 +/- 0.0896, Sum=10.1909 +/- 0.0243 Interval 7, DeltaF=-1.6450 +/- 0.1242, Sum=9.2165 +/- 0.0260 Interval 8, DeltaF=-2.4404 +/- 0.0902, Sum=7.7710 +/- 0.0264 Interval 9, DeltaF=-3.0333 +/- 0.0561, Sum=5.9742 +/- 0.0265 Interval 10, DeltaF=-1.0631 +/- 0.0237, Sum=5.3445 +/- 0.0265 Average EXP free energy: 5.3445 +/- 0.0265 Interval 1, DeltaF=6.8187 +/- 0.1380, Sum=4.0390 +/- 0.0113 Interval 2, DeltaF=2.0890 +/- 0.2015, Sum=5.2763 +/- 0.0266 Interval 3, DeltaF=3.4568 +/- 0.2452, Sum=7.3239 +/- 0.0444 Interval 4, DeltaF=4.1078 +/- 0.3102, Sum=9.7571 +/- 0.0723 Interval 5, DeltaF=1.3851 +/- 0.3431, Sum=10.5776 +/- 0.1004 Interval 6, DeltaF=-0.4611 +/- 0.4409, Sum=10.3044 +/- 0.1528 Interval 7, DeltaF=-1.5363 +/- 0.3995, Sum=9.3944 +/- 0.1797 Interval 8, DeltaF=-2.4321 +/- 0.5060, Sum=7.9538 +/- 0.2351 Interval 9, DeltaF=-3.0350 +/- 0.4357, Sum=6.1561 +/- 0.2606 Interval 10, DeltaF=-1.0728 +/- 0.5203, Sum=5.5206 +/- 0.3060 Double-Wide EXP free energy: 5.5206 +/- 0.3060 Method: BAR Interval 1, DeltaF=6.8324 +/- 0.2854, Sum=4.0471 +/- 0.0482 Interval 2, DeltaF=2.0688 +/- 0.2010, Sum=5.2725 +/- 0.0538 Interval 3, DeltaF=3.3489 +/- 0.2481, Sum=7.2562 +/- 0.0650 Interval 4, DeltaF=3.4926 +/- 0.2785, Sum=9.3249 +/- 0.0796 Interval 5, DeltaF=1.3699 +/- 0.3102, Sum=10.1363 +/- 0.0979 Interval 6, DeltaF=-0.5919 +/- 0.2361, Sum=9.7858 +/- 0.1033 Interval 7, DeltaF=-1.6236 +/- 0.2620, Sum=8.8240 +/- 0.1110 Interval 8, DeltaF=-2.3964 +/- 0.2491, Sum=7.4046 +/- 0.1170 Interval 9, DeltaF=-2.9972 +/- 0.2048, Sum=5.6292 +/- 0.1196 Interval 10, DeltaF=-1.0786 +/- 0.1379, Sum=4.9903 +/- 0.1201 BAR free energy: 4.9903 +/- 0.1201 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.6860 +/- 0.4748, Sum=3.9604 +/- 0.1336 Interval 2, DeltaF=2.0817 +/- 0.2913, Sum=5.1934 +/- 0.1427 Interval 3, DeltaF=3.3616 +/- 0.3152, Sum=7.1846 +/- 0.1544 Interval 4, DeltaF=3.5914 +/- 0.3632, Sum=9.3119 +/- 0.1730 Interval 5, DeltaF=1.3447 +/- 0.3485, Sum=10.1084 +/- 0.1874 Interval 6, DeltaF=-0.6029 +/- 0.2244, Sum=9.7513 +/- 0.1897 Interval 7, DeltaF=-1.5811 +/- 0.2571, Sum=8.8148 +/- 0.1937 Interval 8, DeltaF=-2.4138 +/- 0.3054, Sum=7.3850 +/- 0.2014 Interval 9, DeltaF=-3.0155 +/- 0.4121, Sum=5.5988 +/- 0.2252 Interval 10, DeltaF=-1.0725 +/- 0.1965, Sum=4.9635 +/- 0.2263 Unopt. BAR free energy: 4.9635 +/- 0.2263 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8402 +/- 0.2858, Sum=4.0517 +/- 0.0484 Interval 2, DeltaF=2.0694 +/- 0.2019, Sum=5.2775 +/- 0.0541 Interval 3, DeltaF=3.3445 +/- 0.2477, Sum=7.2585 +/- 0.0652 Interval 4, DeltaF=3.4895 +/- 0.2907, Sum=9.3255 +/- 0.0822 Interval 5, DeltaF=1.3661 +/- 0.3211, Sum=10.1347 +/- 0.1024 Interval 6, DeltaF=-0.5838 +/- 0.2481, Sum=9.7888 +/- 0.1087 Interval 7, DeltaF=-1.6384 +/- 0.2719, Sum=8.8183 +/- 0.1172 Interval 8, DeltaF=-2.3941 +/- 0.2497, Sum=7.4002 +/- 0.1228 Interval 9, DeltaF=-2.9972 +/- 0.2046, Sum=5.6249 +/- 0.1253 Interval 10, DeltaF=-1.0783 +/- 0.1379, Sum=4.9862 +/- 0.1258 Postopt. BAR free energy: 4.9862 +/- 0.1258 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.74845494] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 5.0491277] relative max_delta = 2.576035e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.2290 relative max_delta = 3.440456e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8396 relative max_delta = 2.354799e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8324 relative max_delta = 1.058894e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8324 relative max_delta = 8.093004e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8324 relative max_delta = 1.299953e-15 Converged to tolerance of 1.299953e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8324 Final dimensionless free energies f_k = [ 0. 6.83239019] Computing normalized weights... Interval 1, DeltaF=6.8324 +/- 0.2854, Sum=4.0471 +/- 0.0482 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 882 N_k = [500 382] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.61945616] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.95443544] relative max_delta = 1.713944e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9659 relative max_delta = 5.842988e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 2.0692 relative max_delta = 4.990794e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 2.0688 relative max_delta = 2.062595e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 2.0688 relative max_delta = 2.828780e-09 Converged to tolerance of 2.828780e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 2.0688 Final dimensionless free energies f_k = [ 0. 2.06876466] Computing normalized weights... Interval 2, DeltaF=2.0688 +/- 0.2010, Sum=5.2725 +/- 0.0538 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 882 N_k = [382 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.75461841] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.60507973] relative max_delta = 3.264627e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6805 relative max_delta = 2.814062e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3558 relative max_delta = 2.012244e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3489 relative max_delta = 2.060446e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3489 relative max_delta = 2.410920e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3489 relative max_delta = 3.049994e-15 Converged to tolerance of 3.049994e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3489 Final dimensionless free energies f_k = [ 0. 3.34887555] Computing normalized weights... Interval 3, DeltaF=3.3489 +/- 0.2481, Sum=7.2562 +/- 0.0650 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.06967928] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.86088019] relative max_delta = 4.251756e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0568 relative max_delta = 9.525584e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7436 relative max_delta = 4.505872e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4988 relative max_delta = 6.998261e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4926 relative max_delta = 1.779154e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4926 relative max_delta = 1.156273e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4926 relative max_delta = 4.880120e-13 Converged to tolerance of 4.880120e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4926 Final dimensionless free energies f_k = [ 0. 3.49256624] Computing normalized weights... Interval 4, DeltaF=3.4926 +/- 0.2785, Sum=9.3249 +/- 0.0796 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 968 N_k = [500 468] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.36229843] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.63883669] relative max_delta = 4.328779e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7194 relative max_delta = 1.119324e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.4285 relative max_delta = 4.964249e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3703 relative max_delta = 4.246007e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3699 relative max_delta = 3.295075e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3699 relative max_delta = 1.967341e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3699 relative max_delta = 5.024870e-15 Converged to tolerance of 5.024870e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3699 Final dimensionless free energies f_k = [ 0. 1.36986279] Computing normalized weights... Interval 5, DeltaF=1.3699 +/- 0.3102, Sum=10.1363 +/- 0.0979 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 824 N_k = [468 356] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.37387072] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.50911343] relative max_delta = 2.656436e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5173 relative max_delta = 1.589283e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5914 relative max_delta = 1.252881e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5919 relative max_delta = 7.657976e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5919 relative max_delta = 2.968119e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5919 relative max_delta = 6.189910e-15 Converged to tolerance of 6.189910e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5919 Final dimensionless free energies f_k = [ 0. -0.59188844] Computing normalized weights... Interval 6, DeltaF=-0.5919 +/- 0.2361, Sum=9.7858 +/- 0.1033 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 655 N_k = [356 299] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01249685] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.37063605] relative max_delta = 2.612942e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3955 relative max_delta = 1.782559e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6201 relative max_delta = 1.386343e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6236 relative max_delta = 2.143103e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6236 relative max_delta = 5.809898e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6236 relative max_delta = 4.225915e-14 Converged to tolerance of 4.225915e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6236 Final dimensionless free energies f_k = [ 0. -1.62359591] Computing normalized weights... Interval 7, DeltaF=-1.6236 +/- 0.2620, Sum=8.8240 +/- 0.1110 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 559 N_k = [299 260] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.62496841] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.12598289] relative max_delta = 2.356625e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1530 relative max_delta = 1.256937e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3965 relative max_delta = 1.015868e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3964 relative max_delta = 3.823590e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3964 relative max_delta = 3.317318e-11 Converged to tolerance of 3.317318e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3964 Final dimensionless free energies f_k = [ 0. -2.39640629] Computing normalized weights... Interval 8, DeltaF=-2.3964 +/- 0.2491, Sum=7.4046 +/- 0.1170 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 722 N_k = [260 462] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.41320545] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.86483187] relative max_delta = 1.576450e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8783 relative max_delta = 4.674795e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9989 relative max_delta = 4.023445e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9972 relative max_delta = 5.815356e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9972 relative max_delta = 1.143186e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9972 relative max_delta = 6.223047e-15 Converged to tolerance of 6.223047e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9972 Final dimensionless free energies f_k = [ 0. -2.997205] Computing normalized weights... Interval 9, DeltaF=-2.9972 +/- 0.2048, Sum=5.6292 +/- 0.1196 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 903 N_k = [462 441] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99791379] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07250358] relative max_delta = 6.954736e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0731 relative max_delta = 5.688118e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0786 relative max_delta = 5.093269e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0786 relative max_delta = 1.695859e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0786 relative max_delta = 8.234489e-16 Converged to tolerance of 8.234489e-16 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0786 Final dimensionless free energies f_k = [ 0. -1.0786078] Computing normalized weights... Interval 10, DeltaF=-1.0786 +/- 0.1379, Sum=4.9903 +/- 0.1201 Pairwise MBAR free energy: 4.9903 +/- 0.1201 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4668 N_k = [500 500 382 500 500 468 356 299 260 462 441] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.0137968 1.97602103 1.77420784 1.54196355 1.71006697 1.69521408 1.66593864 1.59510236 0.94104231 0.4445266 ] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.99315936 3.31925226 3.2477672 2.89253216 3.12842234 3.08665528 2.95656185 2.67804262 1.52532995 0.84583881] relative max_delta = 4.439432e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2769 3.7542 4.2179 4.4751 4.8472 4.7562 4.5140 4.0630 2.6876 1.9624 relative max_delta = 3.545967e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.9638 7.8439 12.5158 17.6653 19.2106 18.6719 17.3711 15.2579 11.9064 10.7846 relative max_delta = 7.476792e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8226 9.0487 12.2842 16.2460 17.6137 17.0357 15.4151 13.0463 10.0307 8.9482 relative max_delta = 1.255617e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8163 8.8679 12.2394 15.7360 17.0965 16.5139 14.8864 12.4872 9.5011 8.4181 relative max_delta = 3.270620e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8153 8.8657 12.2309 15.7046 17.0661 16.4834 14.8558 12.4564 9.4706 8.3876 relative max_delta = 1.839722e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8153 8.8657 12.2309 15.7045 17.0660 16.4833 14.8558 12.4563 9.4705 8.3875 relative max_delta = 5.807454e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8153 8.8657 12.2309 15.7045 17.0660 16.4833 14.8558 12.4563 9.4705 8.3875 relative max_delta = 7.231525e-11 Converged to tolerance of 7.231525e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8153 8.8657 12.2309 15.7045 17.0660 16.4833 14.8558 12.4563 9.4705 8.3875 Final dimensionless free energies f_k = [ 0. 6.81531863 8.86572033 12.23085195 15.70454397 17.06596035 16.48326549 14.85575375 12.45633939 9.47049777 8.38748899] Computing normalized weights... DeltaMij: [[ 0. 4.03696774 5.25149724 7.24479037 9.30238788 10.10880564 9.76365372 8.79961773 7.378355 5.6097295 4.96822296] [ -4.03696774 0. 1.2145295 3.20782263 5.26542014 6.0718379 5.72668598 4.76264999 3.34138726 1.57276176 0.93125522] [ -5.25149724 -1.2145295 0. 1.99329313 4.05089064 4.8573084 4.51215648 3.54812049 2.12685776 0.35823226 -0.28327428] [ -7.24479037 -3.20782263 -1.99329313 0. 2.05759751 2.86401527 2.51886335 1.55482736 0.13356463 -1.63506087 -2.27656741] [ -9.30238788 -5.26542014 -4.05089064 -2.05759751 0. 0.80641776 0.46126584 -0.50277015 -1.92403288 -3.69265838 -4.33416492] [-10.10880564 -6.0718379 -4.8573084 -2.86401527 -0.80641776 0. -0.34515192 -1.30918791 -2.73045064 -4.49907614 -5.14058268] [ -9.76365372 -5.72668598 -4.51215648 -2.51886335 -0.46126584 0.34515192 0. -0.96403599 -2.38529872 -4.15392422 -4.79543076] [ -8.79961773 -4.76264999 -3.54812049 -1.55482736 0.50277015 1.30918791 0.96403599 0. -1.42126273 -3.18988823 -3.83139477] [ -7.378355 -3.34138726 -2.12685776 -0.13356463 1.92403288 2.73045064 2.38529872 1.42126273 0. -1.7686255 -2.41013204] [ -5.6097295 -1.57276176 -0.35823226 1.63506087 3.69265838 4.49907614 4.15392422 3.18988823 1.7686255 0. -0.64150654] [ -4.96822296 -0.93125522 0.28327428 2.27656741 4.33416492 5.14058268 4.79543076 3.83139477 2.41013204 0.64150654 0. ]] dDeltaMij: [[ 0. 0.04757168 0.06054657 0.07341521 0.08943015 0.11035771 0.11916253 0.12971707 0.13925104 0.14430641 0.14606003] [ 0.04757168 0. 0.02217248 0.04602947 0.06877801 0.09440102 0.10455829 0.11644417 0.12697866 0.13250309 0.13441078] [ 0.06054657 0.02217248 0. 0.03242039 0.06086663 0.08880276 0.09953296 0.11195365 0.12287373 0.12857466 0.13053978] [ 0.07341521 0.04602947 0.03242039 0. 0.04490993 0.07866856 0.09060774 0.10409879 0.11576223 0.12179648 0.12386918] [ 0.08943015 0.06877801 0.06086663 0.04490993 0. 0.05532543 0.07124721 0.08776969 0.10133027 0.10817262 0.11050116] [ 0.11035771 0.09440102 0.08880276 0.07866856 0.05532543 0. 0.03123859 0.05957388 0.07820943 0.08688957 0.08977177] [ 0.11916253 0.10455829 0.09953296 0.09060774 0.07124721 0.03123859 0. 0.03865062 0.06319995 0.07373452 0.07711116] [ 0.12971707 0.11644417 0.11195365 0.10409879 0.08776969 0.05957388 0.03865062 0. 0.03286791 0.04854681 0.05356221] [ 0.13925104 0.12697866 0.12287373 0.11576223 0.10133027 0.07820943 0.06319995 0.03286791 0. 0.02049467 0.02859911] [ 0.14430641 0.13250309 0.12857466 0.12179648 0.10817262 0.08688957 0.07373452 0.04854681 0.02049467 0. 0.01028791] [ 0.14606003 0.13441078 0.13053978 0.12386918 0.11050116 0.08977177 0.07711116 0.05356221 0.02859911 0.01028791 0. ]] Replica 25 / 40 Computing statistical inefficiencies: lambda 0: g = 2.205 lambda 1: g = 2.274 lambda 2: g = 2.289 lambda 3: g = 1.730 lambda 4: g = 2.105 lambda 5: g = 1.624 lambda 6: g = 2.704 lambda 7: g = 1.949 lambda 8: g = 3.610 lambda 9: g = 1.558 lambda 10: g = 1.259 Subsampling data to produce uncorrelated samples... number of samples per lambda: [314 500 500 371 336 387 269 211 198 304 500] Method: EXP Forward EXP: Interval 1, DeltaF=5.6452 +/- 0.7554, Sum=3.3439 +/- 0.3380 Interval 2, DeltaF=1.8501 +/- 0.2748, Sum=4.4397 +/- 0.3409 Interval 3, DeltaF=2.4984 +/- 0.6057, Sum=5.9197 +/- 0.4043 Interval 4, DeltaF=3.6966 +/- 0.5189, Sum=8.1093 +/- 0.4346 Interval 5, DeltaF=2.0295 +/- 0.5335, Sum=9.3114 +/- 0.4662 Interval 6, DeltaF=-1.3990 +/- 0.8233, Sum=8.4827 +/- 0.6152 Interval 7, DeltaF=-2.3729 +/- 0.7841, Sum=7.0772 +/- 0.7149 Interval 8, DeltaF=-2.1503 +/- 0.3139, Sum=5.8035 +/- 0.7173 Interval 9, DeltaF=-3.0141 +/- 0.3049, Sum=4.0181 +/- 0.7194 Interval 10, DeltaF=-1.1168 +/- 0.1852, Sum=3.3566 +/- 0.7197 Forward EXP free energy: 3.3566 +/- 0.7197 Reverse EXP: Interval 1, DeltaF=6.6086 +/- 0.5047, Sum=3.9145 +/- 0.1509 Interval 2, DeltaF=1.9935 +/- 0.2910, Sum=5.0953 +/- 0.1590 Interval 3, DeltaF=3.2600 +/- 0.3914, Sum=7.0264 +/- 0.1831 Interval 4, DeltaF=3.2334 +/- 0.3905, Sum=8.9416 +/- 0.2041 Interval 5, DeltaF=1.6188 +/- 0.4041, Sum=9.9005 +/- 0.2259 Interval 6, DeltaF=-0.5942 +/- 0.3144, Sum=9.5485 +/- 0.2334 Interval 7, DeltaF=-2.0225 +/- 0.3709, Sum=8.3505 +/- 0.2472 Interval 8, DeltaF=-2.1893 +/- 0.4034, Sum=7.0538 +/- 0.2653 Interval 9, DeltaF=-3.0156 +/- 0.2870, Sum=5.2675 +/- 0.2697 Interval 10, DeltaF=-1.0550 +/- 0.1771, Sum=4.6426 +/- 0.2704 Reverse EXP free energy: 4.6426 +/- 0.2704 Averge of forward and reverse EXP: Interval 1, DeltaF=6.1269 +/- 0.3401, Sum=3.6292 +/- 0.0685 Interval 2, DeltaF=1.9218 +/- 0.0617, Sum=4.7675 +/- 0.0685 Interval 3, DeltaF=2.8792 +/- 0.2163, Sum=6.4730 +/- 0.0739 Interval 4, DeltaF=3.4650 +/- 0.1684, Sum=8.5255 +/- 0.0758 Interval 5, DeltaF=1.8242 +/- 0.1786, Sum=9.6060 +/- 0.0781 Interval 6, DeltaF=-0.9966 +/- 0.3728, Sum=9.0156 +/- 0.1135 Interval 7, DeltaF=-2.1977 +/- 0.3428, Sum=7.7139 +/- 0.1331 Interval 8, DeltaF=-2.1698 +/- 0.1035, Sum=6.4286 +/- 0.1333 Interval 9, DeltaF=-3.0148 +/- 0.0676, Sum=4.6428 +/- 0.1333 Interval 10, DeltaF=-1.0859 +/- 0.0253, Sum=3.9996 +/- 0.1333 Average EXP free energy: 3.9996 +/- 0.1333 Interval 1, DeltaF=6.6086 +/- 0.1960, Sum=3.9145 +/- 0.0228 Interval 2, DeltaF=1.8501 +/- 0.6238, Sum=5.0104 +/- 0.2316 Interval 3, DeltaF=3.2600 +/- 0.3150, Sum=6.9414 +/- 0.2389 Interval 4, DeltaF=3.6966 +/- 0.7712, Sum=9.1310 +/- 0.4257 Interval 5, DeltaF=1.6188 +/- 0.3956, Sum=10.0899 +/- 0.4357 Interval 6, DeltaF=-1.3990 +/- 1.0029, Sum=9.2612 +/- 0.7381 Interval 7, DeltaF=-2.0225 +/- 0.4417, Sum=8.0632 +/- 0.7471 Interval 8, DeltaF=-2.1503 +/- 1.3159, Sum=6.7895 +/- 1.2689 Interval 9, DeltaF=-3.0156 +/- 0.4916, Sum=5.0033 +/- 1.2769 Interval 10, DeltaF=-1.1168 +/- 1.3222, Sum=4.3418 +/- 1.6440 Double-Wide EXP free energy: 4.3418 +/- 1.6440 Method: BAR Interval 1, DeltaF=6.6707 +/- 0.3059, Sum=3.9513 +/- 0.0554 Interval 2, DeltaF=1.9625 +/- 0.1954, Sum=5.1138 +/- 0.0599 Interval 3, DeltaF=3.2371 +/- 0.2586, Sum=7.0312 +/- 0.0718 Interval 4, DeltaF=3.3257 +/- 0.3014, Sum=9.0012 +/- 0.0897 Interval 5, DeltaF=1.5006 +/- 0.3226, Sum=9.8900 +/- 0.1089 Interval 6, DeltaF=-0.4811 +/- 0.2509, Sum=9.6051 +/- 0.1151 Interval 7, DeltaF=-1.7237 +/- 0.2873, Sum=8.5841 +/- 0.1250 Interval 8, DeltaF=-2.3213 +/- 0.2584, Sum=7.2091 +/- 0.1311 Interval 9, DeltaF=-2.9587 +/- 0.2314, Sum=5.4565 +/- 0.1349 Interval 10, DeltaF=-1.0827 +/- 0.1461, Sum=4.8152 +/- 0.1355 BAR free energy: 4.8152 +/- 0.1355 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=5.9153 +/- 0.4159, Sum=3.5038 +/- 0.1024 Interval 2, DeltaF=1.9145 +/- 0.2552, Sum=4.6379 +/- 0.1095 Interval 3, DeltaF=2.9290 +/- 0.3527, Sum=6.3728 +/- 0.1320 Interval 4, DeltaF=3.3202 +/- 0.4015, Sum=8.3395 +/- 0.1629 Interval 5, DeltaF=1.4406 +/- 0.3569, Sum=9.1928 +/- 0.1795 Interval 6, DeltaF=-0.4936 +/- 0.2381, Sum=8.9004 +/- 0.1826 Interval 7, DeltaF=-1.8390 +/- 0.2787, Sum=7.8111 +/- 0.1883 Interval 8, DeltaF=-2.2983 +/- 0.3345, Sum=6.4497 +/- 0.1997 Interval 9, DeltaF=-2.9812 +/- 0.4253, Sum=4.6839 +/- 0.2266 Interval 10, DeltaF=-1.0692 +/- 0.2451, Sum=4.0506 +/- 0.2293 Unopt. BAR free energy: 4.0506 +/- 0.2293 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6889 +/- 0.3095, Sum=3.9621 +/- 0.0568 Interval 2, DeltaF=1.9632 +/- 0.1956, Sum=5.1249 +/- 0.0611 Interval 3, DeltaF=3.2269 +/- 0.2632, Sum=7.0363 +/- 0.0736 Interval 4, DeltaF=3.3253 +/- 0.3102, Sum=9.0060 +/- 0.0931 Interval 5, DeltaF=1.5271 +/- 0.3107, Sum=9.9106 +/- 0.1093 Interval 6, DeltaF=-0.4936 +/- 0.2381, Sum=9.6182 +/- 0.1143 Interval 7, DeltaF=-1.7128 +/- 0.2942, Sum=8.6036 +/- 0.1253 Interval 8, DeltaF=-2.3242 +/- 0.2580, Sum=7.2269 +/- 0.1313 Interval 9, DeltaF=-2.9590 +/- 0.2298, Sum=5.4742 +/- 0.1350 Interval 10, DeltaF=-1.0816 +/- 0.1543, Sum=4.8335 +/- 0.1358 Postopt. BAR free energy: 4.8335 +/- 0.1358 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 814 N_k = [314 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.365958] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.73670795] relative max_delta = 2.893887e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9176 relative max_delta = 3.678635e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5605 relative max_delta = 2.504164e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6701 relative max_delta = 1.644537e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6707 relative max_delta = 8.322064e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6707 relative max_delta = 2.118698e-09 Converged to tolerance of 2.118698e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6707 Final dimensionless free energies f_k = [ 0. 6.67070218] Computing normalized weights... Interval 1, DeltaF=6.6707 +/- 0.3059, Sum=3.9513 +/- 0.0554 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.50542674] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.84267009] relative max_delta = 1.830188e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8547 relative max_delta = 6.460015e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9625 relative max_delta = 5.494352e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9625 relative max_delta = 1.946307e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9625 relative max_delta = 8.593090e-12 Converged to tolerance of 8.593090e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9625 Final dimensionless free energies f_k = [ 0. 1.96251473] Computing normalized weights... Interval 2, DeltaF=1.9625 +/- 0.1954, Sum=5.1138 +/- 0.0599 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 871 N_k = [500 371] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.57417176] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.39132463] relative max_delta = 3.417156e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4831 relative max_delta = 3.696912e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2926 relative max_delta = 2.458422e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2373 relative max_delta = 1.708274e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2371 relative max_delta = 6.299285e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2371 relative max_delta = 8.790487e-10 Converged to tolerance of 8.790487e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2371 Final dimensionless free energies f_k = [ 0. 3.23707278] Computing normalized weights... Interval 3, DeltaF=3.2371 +/- 0.2586, Sum=7.0312 +/- 0.0718 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 707 N_k = [371 336] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.0354477] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.8035752] relative max_delta = 4.258916e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9888 relative max_delta = 9.314141e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5724 relative max_delta = 4.432838e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3315 relative max_delta = 7.232058e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3257 relative max_delta = 1.735173e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3257 relative max_delta = 1.020075e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3257 relative max_delta = 3.542620e-13 Converged to tolerance of 3.542620e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3257 Final dimensionless free energies f_k = [ 0. 3.3256983] Computing normalized weights... Interval 4, DeltaF=3.3257 +/- 0.3014, Sum=9.0012 +/- 0.0897 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 723 N_k = [336 387] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.44164576] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.76490511] relative max_delta = 4.226137e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.8440 relative max_delta = 9.374888e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.5448 relative max_delta = 4.536474e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.5008 relative max_delta = 2.934503e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.5006 relative max_delta = 1.293075e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.5006 relative max_delta = 2.498871e-09 Converged to tolerance of 2.498871e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.5006 Final dimensionless free energies f_k = [ 0. 1.50061364] Computing normalized weights... Interval 5, DeltaF=1.5006 +/- 0.3226, Sum=9.8900 +/- 0.1089 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 656 N_k = [387 269] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.30173534] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.41269362] relative max_delta = 2.688636e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4195 relative max_delta = 1.619944e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4807 relative max_delta = 1.273897e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4811 relative max_delta = 7.338618e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4811 relative max_delta = 2.492866e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4811 relative max_delta = 6.115569e-15 Converged to tolerance of 6.115569e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4811 Final dimensionless free energies f_k = [ 0. -0.48108212] Computing normalized weights... Interval 6, DeltaF=-0.4811 +/- 0.2509, Sum=9.6051 +/- 0.1151 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 480 N_k = [269 211] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.04645565] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.433346] relative max_delta = 2.699211e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4618 relative max_delta = 1.949601e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7193 relative max_delta = 1.497299e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7237 relative max_delta = 2.557140e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7237 relative max_delta = 8.244392e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7237 relative max_delta = 8.592290e-14 Converged to tolerance of 8.592290e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7237 Final dimensionless free energies f_k = [ 0. -1.72368188] Computing normalized weights... Interval 7, DeltaF=-1.7237 +/- 0.2873, Sum=8.5841 +/- 0.1250 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 409 N_k = [211 198] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.6940815] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.12833979] relative max_delta = 2.040362e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1476 relative max_delta = 8.973881e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3211 relative max_delta = 7.473101e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3213 relative max_delta = 8.707413e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3213 relative max_delta = 3.014211e-10 Converged to tolerance of 3.014211e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3213 Final dimensionless free energies f_k = [ 0. -2.32127008] Computing normalized weights... Interval 8, DeltaF=-2.3213 +/- 0.2584, Sum=7.2091 +/- 0.1311 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 502 N_k = [198 304] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.27977533] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.78406561] relative max_delta = 1.811345e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8018 relative max_delta = 6.342455e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9611 relative max_delta = 5.379998e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9587 relative max_delta = 8.226185e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9587 relative max_delta = 1.733669e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9587 relative max_delta = 7.354679e-15 Converged to tolerance of 7.354679e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9587 Final dimensionless free energies f_k = [ 0. -2.95871131] Computing normalized weights... Interval 9, DeltaF=-2.9587 +/- 0.2314, Sum=5.4565 +/- 0.1349 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 804 N_k = [304 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00488108] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07657084] relative max_delta = 6.659084e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0772 relative max_delta = 5.711806e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0827 relative max_delta = 5.113608e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0827 relative max_delta = 3.100063e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0827 relative max_delta = 1.136761e-12 Converged to tolerance of 1.136761e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0827 Final dimensionless free energies f_k = [ 0. -1.08271937] Computing normalized weights... Interval 10, DeltaF=-1.0827 +/- 0.1461, Sum=4.8152 +/- 0.1355 Pairwise MBAR free energy: 4.8152 +/- 0.1355 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3890 N_k = [314 500 500 371 336 387 269 211 198 304 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.18252824 2.33988903 2.06711235 1.76143316 1.94773318 1.98771607 1.97056647 1.8890084 1.30693451 0.85877655] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.26914453 3.85111589 3.73277379 3.24383988 3.51806606 3.55113126 3.44736894 3.16893055 2.13445295 1.5040747 ] relative max_delta = 4.325140e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.5050 4.2138 4.6150 4.7655 5.1810 5.1662 4.9443 4.4903 3.2332 2.5496 relative max_delta = 3.209693e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7522 7.6163 12.1447 17.4256 19.0696 18.6165 17.2698 15.1411 11.9138 10.7684 relative max_delta = 7.283110e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6475 8.7003 11.9887 15.9683 17.4417 16.9352 15.2292 12.9319 10.0065 8.9201 relative max_delta = 1.266619e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6812 8.6393 11.8678 15.2477 16.7174 16.2053 14.4904 12.1731 9.2724 8.1852 relative max_delta = 4.539365e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6803 8.6395 11.8545 15.1796 16.6517 16.1396 14.4247 12.1072 9.2067 8.1195 relative max_delta = 4.087694e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6803 8.6395 11.8544 15.1791 16.6512 16.1391 14.4242 12.1067 9.2062 8.1190 relative max_delta = 3.266837e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6803 8.6395 11.8544 15.1791 16.6512 16.1391 14.4242 12.1067 9.2062 8.1190 relative max_delta = 2.093040e-09 Converged to tolerance of 2.093040e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6803 8.6395 11.8544 15.1791 16.6512 16.1391 14.4242 12.1067 9.2062 8.1190 Final dimensionless free energies f_k = [ 0. 6.68033846 8.63949886 11.85442416 15.17905062 16.65121236 16.13909429 14.4241942 12.10669411 9.20619999 8.11900188] Computing normalized weights... DeltaMij: [[ 0. 3.95701395 5.11749782 7.02181813 8.99111855 9.86313492 9.55978826 8.5439889 7.17124705 5.45317606 4.80918802] [-3.95701395 0. 1.16048387 3.06480419 5.0341046 5.90612097 5.60277431 4.58697495 3.2142331 1.49616211 0.85217407] [-5.11749782 -1.16048387 0. 1.90432032 3.87362073 4.7456371 4.44229045 3.42649108 2.05374923 0.33567824 -0.3083098 ] [-7.02181813 -3.06480419 -1.90432032 0. 1.96930041 2.84131679 2.53797013 1.52217076 0.14942891 -1.56864208 -2.21263012] [-8.99111855 -5.0341046 -3.87362073 -1.96930041 0. 0.87201637 0.56866972 -0.44712965 -1.8198715 -3.53794249 -4.18193053] [-9.86313492 -5.90612097 -4.7456371 -2.84131679 -0.87201637 0. -0.30334666 -1.31914602 -2.69188787 -4.40995886 -5.0539469 ] [-9.55978826 -5.60277431 -4.44229045 -2.53797013 -0.56866972 0.30334666 0. -1.01579937 -2.38854121 -4.1066122 -4.75060025] [-8.5439889 -4.58697495 -3.42649108 -1.52217076 0.44712965 1.31914602 1.01579937 0. -1.37274185 -3.09081284 -3.73480088] [-7.17124705 -3.2142331 -2.05374923 -0.14942891 1.8198715 2.69188787 2.38854121 1.37274185 0. -1.71807099 -2.36205903] [-5.45317606 -1.49616211 -0.33567824 1.56864208 3.53794249 4.40995886 4.1066122 3.09081284 1.71807099 0. -0.64398804] [-4.80918802 -0.85217407 0.3083098 2.21263012 4.18193053 5.0539469 4.75060025 3.73480088 2.36205903 0.64398804 0. ]] dDeltaMij: [[ 0. 0.0541401 0.06567386 0.07888181 0.09887778 0.12244586 0.13254875 0.14612389 0.15664645 0.16309368 0.16519272] [ 0.0541401 0. 0.02120637 0.047758 0.07640859 0.10514038 0.1167505 0.13196097 0.14352567 0.1505359 0.15280754] [ 0.06567386 0.02120637 0. 0.03614067 0.06995782 0.10055052 0.11263475 0.12833396 0.14019816 0.14736676 0.14968651] [ 0.07888181 0.047758 0.03614067 0. 0.05127028 0.0884936 0.10201718 0.11912391 0.13181967 0.13941974 0.14186949] [ 0.09887778 0.07640859 0.06995782 0.05127028 0. 0.06032025 0.07877204 0.09994464 0.1147815 0.12343515 0.12619558] [ 0.12244586 0.10514038 0.10055052 0.0884936 0.06032025 0. 0.03645679 0.07105879 0.09077443 0.10149362 0.10483325] [ 0.13254875 0.1167505 0.11263475 0.10201718 0.07877204 0.03645679 0. 0.04690294 0.07275562 0.08582563 0.08975248] [ 0.14612389 0.13196097 0.12833396 0.11912391 0.09994464 0.07105879 0.04690294 0. 0.03546685 0.05557879 0.06149148] [ 0.15664645 0.14352567 0.14019816 0.13181967 0.1147815 0.09077443 0.07275562 0.03546685 0. 0.02526203 0.03424108] [ 0.16309368 0.1505359 0.14736676 0.13941974 0.12343515 0.10149362 0.08582563 0.05557879 0.02526203 0. 0.0115381 ] [ 0.16519272 0.15280754 0.14968651 0.14186949 0.12619558 0.10483325 0.08975248 0.06149148 0.03424108 0.0115381 0. ]] Replica 26 / 40 Computing statistical inefficiencies: lambda 0: g = 3.312 lambda 1: g = 1.491 lambda 2: g = 1.624 lambda 3: g = 1.714 lambda 4: g = 2.353 lambda 5: g = 1.465 lambda 6: g = 1.856 lambda 7: g = 1.317 lambda 8: g = 1.469 lambda 9: g = 1.744 lambda 10: g = 1.883 Subsampling data to produce uncorrelated samples... number of samples per lambda: [236 407 500 352 388 317 275 186 399 327 301] Method: EXP Forward EXP: Interval 1, DeltaF=7.3378 +/- 0.3933, Sum=4.3464 +/- 0.0916 Interval 2, DeltaF=1.9175 +/- 0.2611, Sum=5.4823 +/- 0.1001 Interval 3, DeltaF=3.4284 +/- 0.3498, Sum=7.5131 +/- 0.1236 Interval 4, DeltaF=4.2534 +/- 0.4339, Sum=10.0325 +/- 0.1665 Interval 5, DeltaF=1.3061 +/- 0.6051, Sum=10.8061 +/- 0.2734 Interval 6, DeltaF=-0.5024 +/- 0.4529, Sum=10.5085 +/- 0.2992 Interval 7, DeltaF=-1.4908 +/- 0.4569, Sum=9.6255 +/- 0.3238 Interval 8, DeltaF=-2.2497 +/- 0.3384, Sum=8.2930 +/- 0.3308 Interval 9, DeltaF=-2.9148 +/- 0.2533, Sum=6.5664 +/- 0.3330 Interval 10, DeltaF=-1.0764 +/- 0.1809, Sum=5.9288 +/- 0.3335 Forward EXP free energy: 5.9288 +/- 0.3335 Reverse EXP: Interval 1, DeltaF=6.3192 +/- 0.5104, Sum=3.7431 +/- 0.1543 Interval 2, DeltaF=1.9043 +/- 0.2831, Sum=4.8711 +/- 0.1614 Interval 3, DeltaF=3.5962 +/- 0.4591, Sum=7.0012 +/- 0.2041 Interval 4, DeltaF=3.4985 +/- 0.3824, Sum=9.0736 +/- 0.2217 Interval 5, DeltaF=1.1126 +/- 0.4511, Sum=9.7326 +/- 0.2523 Interval 6, DeltaF=-0.4361 +/- 0.3074, Sum=9.4743 +/- 0.2585 Interval 7, DeltaF=-1.7701 +/- 0.3812, Sum=8.4258 +/- 0.2724 Interval 8, DeltaF=-2.4416 +/- 0.2868, Sum=6.9796 +/- 0.2768 Interval 9, DeltaF=-2.9202 +/- 0.2901, Sum=5.2499 +/- 0.2812 Interval 10, DeltaF=-1.1216 +/- 0.1865, Sum=4.5855 +/- 0.2820 Reverse EXP free energy: 4.5855 +/- 0.2820 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8285 +/- 0.1649, Sum=4.0448 +/- 0.0161 Interval 2, DeltaF=1.9109 +/- 0.0572, Sum=5.1767 +/- 0.0162 Interval 3, DeltaF=3.5123 +/- 0.1327, Sum=7.2571 +/- 0.0193 Interval 4, DeltaF=3.8760 +/- 0.1297, Sum=9.5530 +/- 0.0217 Interval 5, DeltaF=1.2093 +/- 0.2280, Sum=10.2694 +/- 0.0377 Interval 6, DeltaF=-0.4692 +/- 0.1229, Sum=9.9914 +/- 0.0387 Interval 7, DeltaF=-1.6304 +/- 0.1384, Sum=9.0257 +/- 0.0403 Interval 8, DeltaF=-2.3456 +/- 0.0767, Sum=7.6363 +/- 0.0405 Interval 9, DeltaF=-2.9175 +/- 0.0576, Sum=5.9081 +/- 0.0405 Interval 10, DeltaF=-1.0990 +/- 0.0260, Sum=5.2572 +/- 0.0405 Average EXP free energy: 5.2572 +/- 0.0405 Interval 1, DeltaF=6.3192 +/- 0.2005, Sum=3.7431 +/- 0.0238 Interval 2, DeltaF=1.9175 +/- 0.1764, Sum=4.8789 +/- 0.0301 Interval 3, DeltaF=3.5962 +/- 0.3381, Sum=7.0091 +/- 0.0741 Interval 4, DeltaF=4.2534 +/- 0.2694, Sum=9.5285 +/- 0.0857 Interval 5, DeltaF=1.1126 +/- 0.4364, Sum=10.1876 +/- 0.1417 Interval 6, DeltaF=-0.5024 +/- 0.5267, Sum=9.8900 +/- 0.2169 Interval 7, DeltaF=-1.7701 +/- 0.4879, Sum=8.8415 +/- 0.2588 Interval 8, DeltaF=-2.2497 +/- 0.6014, Sum=7.5090 +/- 0.3359 Interval 9, DeltaF=-2.9202 +/- 0.5126, Sum=5.7793 +/- 0.3703 Interval 10, DeltaF=-1.0764 +/- 0.6123, Sum=5.1417 +/- 0.4318 Double-Wide EXP free energy: 5.1417 +/- 0.4318 Method: BAR Interval 1, DeltaF=6.6649 +/- 0.3340, Sum=3.9479 +/- 0.0661 Interval 2, DeltaF=1.8914 +/- 0.1987, Sum=5.0682 +/- 0.0701 Interval 3, DeltaF=3.2301 +/- 0.2497, Sum=6.9815 +/- 0.0792 Interval 4, DeltaF=3.4367 +/- 0.3039, Sum=9.0172 +/- 0.0963 Interval 5, DeltaF=1.1609 +/- 0.3386, Sum=9.7049 +/- 0.1178 Interval 6, DeltaF=-0.4832 +/- 0.2475, Sum=9.4186 +/- 0.1233 Interval 7, DeltaF=-1.5791 +/- 0.2921, Sum=8.4833 +/- 0.1332 Interval 8, DeltaF=-2.3616 +/- 0.2406, Sum=7.0844 +/- 0.1376 Interval 9, DeltaF=-2.9216 +/- 0.2031, Sum=5.3538 +/- 0.1397 Interval 10, DeltaF=-1.0891 +/- 0.1528, Sum=4.7087 +/- 0.1404 BAR free energy: 4.7087 +/- 0.1404 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=7.2578 +/- 0.4296, Sum=4.2991 +/- 0.1093 Interval 2, DeltaF=1.9023 +/- 0.2407, Sum=5.4259 +/- 0.1146 Interval 3, DeltaF=3.3028 +/- 0.3631, Sum=7.3822 +/- 0.1386 Interval 4, DeltaF=3.5992 +/- 0.3933, Sum=9.5142 +/- 0.1662 Interval 5, DeltaF=1.1428 +/- 0.3757, Sum=10.1911 +/- 0.1860 Interval 6, DeltaF=-0.4768 +/- 0.2397, Sum=9.9087 +/- 0.1891 Interval 7, DeltaF=-1.6433 +/- 0.2691, Sum=8.9353 +/- 0.1939 Interval 8, DeltaF=-2.4108 +/- 0.3876, Sum=7.5073 +/- 0.2134 Interval 9, DeltaF=-2.9086 +/- 0.3243, Sum=5.7845 +/- 0.2223 Interval 10, DeltaF=-1.0974 +/- 0.2132, Sum=5.1345 +/- 0.2239 Unopt. BAR free energy: 5.1345 +/- 0.2239 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6628 +/- 0.3412, Sum=3.9466 +/- 0.0689 Interval 2, DeltaF=1.8910 +/- 0.2008, Sum=5.0667 +/- 0.0730 Interval 3, DeltaF=3.2306 +/- 0.2541, Sum=6.9804 +/- 0.0824 Interval 4, DeltaF=3.4474 +/- 0.3167, Sum=9.0224 +/- 0.1016 Interval 5, DeltaF=1.1608 +/- 0.3437, Sum=9.7099 +/- 0.1233 Interval 6, DeltaF=-0.4768 +/- 0.2397, Sum=9.4275 +/- 0.1279 Interval 7, DeltaF=-1.5669 +/- 0.3067, Sum=8.4994 +/- 0.1396 Interval 8, DeltaF=-2.3687 +/- 0.2574, Sum=7.0963 +/- 0.1450 Interval 9, DeltaF=-2.9217 +/- 0.2038, Sum=5.3657 +/- 0.1470 Interval 10, DeltaF=-1.0896 +/- 0.1523, Sum=4.7202 +/- 0.1477 Postopt. BAR free energy: 4.7202 +/- 0.1477 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 643 N_k = [236 407] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.42077566] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.75707101] relative max_delta = 2.809072e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9285 relative max_delta = 3.478910e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.4922 relative max_delta = 2.408529e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6624 relative max_delta = 2.555003e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6649 relative max_delta = 3.708816e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6649 relative max_delta = 7.706661e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6649 relative max_delta = 2.931770e-15 Converged to tolerance of 2.931770e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6649 Final dimensionless free energies f_k = [ 0. 6.66489122] Computing normalized weights... Interval 1, DeltaF=6.6649 +/- 0.3340, Sum=3.9479 +/- 0.0661 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 907 N_k = [407 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.45655346] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.78018545] relative max_delta = 1.817968e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7913 relative max_delta = 6.180849e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.8910 relative max_delta = 5.273501e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.8914 relative max_delta = 1.987261e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.8914 relative max_delta = 3.368643e-09 Converged to tolerance of 3.368643e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.8914 Final dimensionless free energies f_k = [ 0. 1.89135354] Computing normalized weights... Interval 2, DeltaF=1.8914 +/- 0.1987, Sum=5.0682 +/- 0.0701 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 852 N_k = [500 352] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.75874584] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.563391] relative max_delta = 3.138987e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6342 relative max_delta = 2.687424e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2618 relative max_delta = 1.924125e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2302 relative max_delta = 9.777987e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2301 relative max_delta = 1.823221e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2301 relative max_delta = 6.476407e-11 Converged to tolerance of 6.476407e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2301 Final dimensionless free energies f_k = [ 0. 3.2301483] Computing normalized weights... Interval 3, DeltaF=3.2301 +/- 0.2497, Sum=6.9815 +/- 0.0792 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 740 N_k = [352 388] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.96813817] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.71240034] relative max_delta = 4.346309e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9257 relative max_delta = 1.107815e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7502 relative max_delta = 4.864914e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4470 relative max_delta = 8.795017e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4367 relative max_delta = 2.982548e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4367 relative max_delta = 3.501489e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4367 relative max_delta = 4.828770e-12 Converged to tolerance of 4.828770e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4367 Final dimensionless free energies f_k = [ 0. 3.43672809] Computing normalized weights... Interval 4, DeltaF=3.4367 +/- 0.3039, Sum=9.0172 +/- 0.0963 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 705 N_k = [388 317] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.31108565] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.5462918] relative max_delta = 4.305504e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6130 relative max_delta = 1.088180e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2022 relative max_delta = 4.901192e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.1611 relative max_delta = 3.541136e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.1609 relative max_delta = 1.877634e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.1609 relative max_delta = 5.251179e-09 Converged to tolerance of 5.251179e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.1609 Final dimensionless free energies f_k = [ 0. 1.1609009] Computing normalized weights... Interval 5, DeltaF=1.1609 +/- 0.3386, Sum=9.7049 +/- 0.1178 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 592 N_k = [317 275] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.31842765] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.42536665] relative max_delta = 2.514043e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4311 relative max_delta = 1.336731e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4830 relative max_delta = 1.074597e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4832 relative max_delta = 3.609759e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4832 relative max_delta = 4.245656e-09 Converged to tolerance of 4.245656e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4832 Final dimensionless free energies f_k = [ 0. -0.48321109] Computing normalized weights... Interval 6, DeltaF=-0.4832 +/- 0.2475, Sum=9.4186 +/- 0.1233 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 461 N_k = [275 186] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.94921916] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.30847724] relative max_delta = 2.745620e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3349 relative max_delta = 1.979691e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5739 relative max_delta = 1.518286e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5791 relative max_delta = 3.331817e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5791 relative max_delta = 1.731781e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5791 relative max_delta = 4.671144e-13 Converged to tolerance of 4.671144e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5791 Final dimensionless free energies f_k = [ 0. -1.57912545] Computing normalized weights... Interval 7, DeltaF=-1.5791 +/- 0.2921, Sum=8.4833 +/- 0.1332 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 585 N_k = [186 399] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.81466729] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.2039631] relative max_delta = 1.766345e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2200 relative max_delta = 7.231303e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3639 relative max_delta = 6.087258e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3616 relative max_delta = 9.870314e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3616 relative max_delta = 2.464994e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3616 relative max_delta = 1.241112e-14 Converged to tolerance of 1.241112e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3616 Final dimensionless free energies f_k = [ 0. -2.36158274] Computing normalized weights... Interval 8, DeltaF=-2.3616 +/- 0.2406, Sum=7.0844 +/- 0.1376 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 726 N_k = [399 327] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.24317555] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.75688788] relative max_delta = 1.863378e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7734 relative max_delta = 5.937684e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9215 relative max_delta = 5.072287e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9216 relative max_delta = 2.972454e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9216 relative max_delta = 4.220900e-11 Converged to tolerance of 4.220900e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9216 Final dimensionless free energies f_k = [ 0. -2.92163115] Computing normalized weights... Interval 9, DeltaF=-2.9216 +/- 0.2031, Sum=5.3538 +/- 0.1397 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 628 N_k = [327 301] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00303652] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08227755] relative max_delta = 7.321692e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0830 relative max_delta = 6.280027e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0891 relative max_delta = 5.620362e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0891 relative max_delta = 4.592565e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0891 relative max_delta = 6.932018e-15 Converged to tolerance of 6.932018e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0891 Final dimensionless free energies f_k = [ 0. -1.08907916] Computing normalized weights... Interval 10, DeltaF=-1.0891 +/- 0.1528, Sum=4.7087 +/- 0.1404 Pairwise MBAR free energy: 4.7087 +/- 0.1404 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3688 N_k = [236 407 500 352 388 317 275 186 399 327 301] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.13462882 2.29365329 2.20769486 1.91519387 2.08789319 2.15596404 2.21047918 2.09402179 1.20298578 0.69837966] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.20965574 3.78798532 3.94759565 3.50443054 3.78402051 3.86248754 3.84139867 3.44994455 1.96613801 1.25769834] relative max_delta = 4.407495e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.4344 4.1310 4.8178 4.9780 5.3619 5.3899 5.2550 4.6808 3.0268 2.2808 relative max_delta = 2.927397e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5919 7.3644 12.0403 17.1332 18.4202 17.9828 16.7613 14.4888 11.3560 10.2770 relative max_delta = 7.089144e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5885 8.6362 11.7930 15.8265 16.9978 16.4930 14.8944 12.5483 9.6150 8.5311 relative max_delta = 1.141624e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6805 8.5864 11.7989 15.2559 16.4271 15.9168 14.3062 11.9589 9.0282 7.9456 relative max_delta = 3.588232e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6787 8.5872 11.7867 15.1969 16.3693 15.8590 14.2484 11.9011 8.9704 7.8878 relative max_delta = 3.606623e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6787 8.5872 11.7866 15.1964 16.3689 15.8586 14.2480 11.9007 8.9700 7.8874 relative max_delta = 2.800225e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6787 8.5872 11.7866 15.1964 16.3689 15.8586 14.2480 11.9007 8.9700 7.8874 relative max_delta = 1.740567e-09 Converged to tolerance of 1.740567e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6787 8.5872 11.7866 15.1964 16.3689 15.8586 14.2480 11.9007 8.9700 7.8874 Final dimensionless free energies f_k = [ 0. 6.67872584 8.5872165 11.78663427 15.19639293 16.36888085 15.85859599 14.24797139 11.90065725 8.96996471 7.88737831] Computing normalized weights... DeltaMij: [[ 0. 3.95605873 5.08652902 6.98166365 9.00139104 9.69589942 9.39363864 8.43960555 7.04920372 5.31324508 4.67198873] [-3.95605873 0. 1.13047029 3.02560492 5.04533231 5.73984069 5.43757991 4.48354681 3.09314498 1.35718634 0.71592999] [-5.08652902 -1.13047029 0. 1.89513463 3.91486202 4.6093704 4.30710962 3.35307652 1.96267469 0.22671605 -0.4145403 ] [-6.98166365 -3.02560492 -1.89513463 0. 2.01972739 2.71423577 2.41197499 1.45794189 0.06754006 -1.66841857 -2.30967493] [-9.00139104 -5.04533231 -3.91486202 -2.01972739 0. 0.69450838 0.3922476 -0.5617855 -1.95218732 -3.68814596 -4.32940231] [-9.69589942 -5.73984069 -4.6093704 -2.71423577 -0.69450838 0. -0.30226078 -1.25629388 -2.64669571 -4.38265434 -5.0239107 ] [-9.39363864 -5.43757991 -4.30710962 -2.41197499 -0.3922476 0.30226078 0. -0.9540331 -2.34443493 -4.08039357 -4.72164992] [-8.43960555 -4.48354681 -3.35307652 -1.45794189 0.5617855 1.25629388 0.9540331 0. -1.39040183 -3.12636047 -3.76761682] [-7.04920372 -3.09314498 -1.96267469 -0.06754006 1.95218732 2.64669571 2.34443493 1.39040183 0. -1.73595864 -2.37721499] [-5.31324508 -1.35718634 -0.22671605 1.66841857 3.68814596 4.38265434 4.08039357 3.12636047 1.73595864 0. -0.64125635] [-4.67198873 -0.71592999 0.4145403 2.30967493 4.32940231 5.0239107 4.72164992 3.76761682 2.37721499 0.64125635 0. ]] dDeltaMij: [[ 0. 0.06450183 0.07602876 0.08696314 0.1059846 0.13032632 0.14032916 0.15295014 0.16229599 0.16674505 0.16854091] [ 0.06450183 0. 0.02271885 0.04696382 0.07666374 0.10784045 0.11973673 0.13430695 0.14486063 0.14982831 0.15182441] [ 0.07602876 0.02271885 0. 0.03374034 0.06966902 0.10298569 0.11538358 0.13044095 0.14128371 0.14637284 0.14841542] [ 0.08696314 0.04696382 0.03374034 0. 0.05356437 0.09279896 0.10639154 0.12255863 0.13404052 0.13939434 0.14153767] [ 0.1059846 0.07666374 0.06966902 0.05356437 0. 0.06506389 0.08326587 0.10312754 0.11653965 0.12265975 0.12509014] [ 0.13032632 0.10784045 0.10298569 0.09279896 0.06506389 0. 0.03555453 0.06991034 0.08854462 0.09645584 0.0995281 ] [ 0.14032916 0.11973673 0.11538358 0.10639154 0.08326587 0.03555453 0. 0.04614435 0.07050817 0.08026302 0.08393005] [ 0.15295014 0.13430695 0.13044095 0.12255863 0.10312754 0.06991034 0.04614435 0. 0.03260099 0.0485924 0.05453046] [ 0.16229599 0.14486063 0.14128371 0.13404052 0.11653965 0.08854462 0.07050817 0.03260099 0. 0.02167852 0.03119732] [ 0.16674505 0.14982831 0.14637284 0.13939434 0.12265975 0.09645584 0.08026302 0.0485924 0.02167852 0. 0.01205158] [ 0.16854091 0.15182441 0.14841542 0.14153767 0.12509014 0.0995281 0.08393005 0.05453046 0.03119732 0.01205158 0. ]] Replica 27 / 40 Computing statistical inefficiencies: lambda 0: g = 1.000 lambda 1: g = 1.297 lambda 2: g = 1.514 lambda 3: g = 1.899 lambda 4: g = 1.452 lambda 5: g = 2.345 lambda 6: g = 1.474 lambda 7: g = 3.000 lambda 8: g = 2.400 lambda 9: g = 1.000 lambda 10: g = 1.297 Subsampling data to produce uncorrelated samples... number of samples per lambda: [300 353 461 334 379 411 323 276 317 313 500] Method: EXP Forward EXP: Interval 1, DeltaF=7.0036 +/- 0.4761, Sum=4.1485 +/- 0.1343 Interval 2, DeltaF=1.9393 +/- 0.2765, Sum=5.2972 +/- 0.1417 Interval 3, DeltaF=3.3849 +/- 0.4101, Sum=7.3022 +/- 0.1732 Interval 4, DeltaF=3.5523 +/- 0.4738, Sum=9.4064 +/- 0.2184 Interval 5, DeltaF=1.7305 +/- 0.4788, Sum=10.4314 +/- 0.2572 Interval 6, DeltaF=-0.1474 +/- 0.3050, Sum=10.3441 +/- 0.2630 Interval 7, DeltaF=-1.6595 +/- 0.4814, Sum=9.3612 +/- 0.2967 Interval 8, DeltaF=-2.3120 +/- 0.2911, Sum=7.9917 +/- 0.3009 Interval 9, DeltaF=-2.8306 +/- 0.2618, Sum=6.3150 +/- 0.3036 Interval 10, DeltaF=-1.0360 +/- 0.1895, Sum=5.7013 +/- 0.3043 Forward EXP free energy: 5.7013 +/- 0.3043 Reverse EXP: Interval 1, DeltaF=6.8279 +/- 0.5137, Sum=4.0444 +/- 0.1563 Interval 2, DeltaF=2.1966 +/- 0.3620, Sum=5.3455 +/- 0.1745 Interval 3, DeltaF=2.8912 +/- 0.3553, Sum=7.0581 +/- 0.1899 Interval 4, DeltaF=3.4072 +/- 0.4072, Sum=9.0763 +/- 0.2138 Interval 5, DeltaF=1.1729 +/- 0.4022, Sum=9.7710 +/- 0.2342 Interval 6, DeltaF=-0.6489 +/- 0.2905, Sum=9.3866 +/- 0.2395 Interval 7, DeltaF=-1.8832 +/- 0.3544, Sum=8.2711 +/- 0.2508 Interval 8, DeltaF=-2.3568 +/- 0.3196, Sum=6.8751 +/- 0.2580 Interval 9, DeltaF=-2.8323 +/- 0.3001, Sum=5.1974 +/- 0.2635 Interval 10, DeltaF=-1.1003 +/- 0.1696, Sum=4.5457 +/- 0.2640 Reverse EXP free energy: 4.5457 +/- 0.2640 Averge of forward and reverse EXP: Interval 1, DeltaF=6.9157 +/- 0.1893, Sum=4.0965 +/- 0.0212 Interval 2, DeltaF=2.0679 +/- 0.0826, Sum=5.3214 +/- 0.0216 Interval 3, DeltaF=3.1381 +/- 0.1144, Sum=7.1802 +/- 0.0230 Interval 4, DeltaF=3.4797 +/- 0.1519, Sum=9.2413 +/- 0.0267 Interval 5, DeltaF=1.4517 +/- 0.1527, Sum=10.1012 +/- 0.0301 Interval 6, DeltaF=-0.3981 +/- 0.0683, Sum=9.8654 +/- 0.0302 Interval 7, DeltaF=-1.7713 +/- 0.1434, Sum=8.8161 +/- 0.0326 Interval 8, DeltaF=-2.3344 +/- 0.0722, Sum=7.4334 +/- 0.0327 Interval 9, DeltaF=-2.8315 +/- 0.0616, Sum=5.7562 +/- 0.0328 Interval 10, DeltaF=-1.0682 +/- 0.0250, Sum=5.1235 +/- 0.0328 Average EXP free energy: 5.1235 +/- 0.0328 Interval 1, DeltaF=6.8279 +/- 0.2031, Sum=4.0444 +/- 0.0244 Interval 2, DeltaF=1.9393 +/- 0.2537, Sum=5.1931 +/- 0.0453 Interval 3, DeltaF=2.8912 +/- 0.3351, Sum=6.9056 +/- 0.0804 Interval 4, DeltaF=3.5523 +/- 0.3622, Sum=9.0098 +/- 0.1118 Interval 5, DeltaF=1.1729 +/- 0.4120, Sum=9.7045 +/- 0.1504 Interval 6, DeltaF=-0.1474 +/- 0.4779, Sum=9.6172 +/- 0.2023 Interval 7, DeltaF=-1.8832 +/- 0.4506, Sum=8.5017 +/- 0.2354 Interval 8, DeltaF=-2.3120 +/- 0.5490, Sum=7.1322 +/- 0.2954 Interval 9, DeltaF=-2.8323 +/- 0.4791, Sum=5.4545 +/- 0.3252 Interval 10, DeltaF=-1.0360 +/- 0.5586, Sum=4.8408 +/- 0.3740 Double-Wide EXP free energy: 4.8408 +/- 0.3740 Method: BAR Interval 1, DeltaF=6.8625 +/- 0.3149, Sum=4.0649 +/- 0.0587 Interval 2, DeltaF=2.0188 +/- 0.2100, Sum=5.2607 +/- 0.0643 Interval 3, DeltaF=3.2078 +/- 0.2650, Sum=7.1608 +/- 0.0766 Interval 4, DeltaF=3.3278 +/- 0.3025, Sum=9.1320 +/- 0.0938 Interval 5, DeltaF=1.2446 +/- 0.3262, Sum=9.8692 +/- 0.1130 Interval 6, DeltaF=-0.5103 +/- 0.2405, Sum=9.5670 +/- 0.1181 Interval 7, DeltaF=-1.7260 +/- 0.2687, Sum=8.5446 +/- 0.1256 Interval 8, DeltaF=-2.3272 +/- 0.2344, Sum=7.1661 +/- 0.1298 Interval 9, DeltaF=-2.8252 +/- 0.2131, Sum=5.4927 +/- 0.1325 Interval 10, DeltaF=-1.0587 +/- 0.1475, Sum=4.8655 +/- 0.1331 BAR free energy: 4.8655 +/- 0.1331 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9556 +/- 0.4815, Sum=4.1201 +/- 0.1373 Interval 2, DeltaF=1.9636 +/- 0.2499, Sum=5.2832 +/- 0.1422 Interval 3, DeltaF=3.2596 +/- 0.3661, Sum=7.2139 +/- 0.1629 Interval 4, DeltaF=3.0927 +/- 0.3925, Sum=9.0459 +/- 0.1867 Interval 5, DeltaF=1.1874 +/- 0.3597, Sum=9.7492 +/- 0.2019 Interval 6, DeltaF=-0.5322 +/- 0.2287, Sum=9.4340 +/- 0.2042 Interval 7, DeltaF=-1.7883 +/- 0.2693, Sum=8.3747 +/- 0.2087 Interval 8, DeltaF=-2.3494 +/- 0.3237, Sum=6.9830 +/- 0.2177 Interval 9, DeltaF=-2.8219 +/- 0.3474, Sum=5.3116 +/- 0.2292 Interval 10, DeltaF=-1.0745 +/- 0.2404, Sum=4.6751 +/- 0.2317 Unopt. BAR free energy: 4.6751 +/- 0.2317 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8665 +/- 0.3152, Sum=4.0673 +/- 0.0589 Interval 2, DeltaF=2.0183 +/- 0.2096, Sum=5.2628 +/- 0.0644 Interval 3, DeltaF=3.2137 +/- 0.2686, Sum=7.1664 +/- 0.0772 Interval 4, DeltaF=3.3070 +/- 0.3109, Sum=9.1253 +/- 0.0961 Interval 5, DeltaF=1.2361 +/- 0.3329, Sum=9.8575 +/- 0.1164 Interval 6, DeltaF=-0.4871 +/- 0.2566, Sum=9.5689 +/- 0.1228 Interval 7, DeltaF=-1.7194 +/- 0.2746, Sum=8.5505 +/- 0.1307 Interval 8, DeltaF=-2.3268 +/- 0.2384, Sum=7.1722 +/- 0.1349 Interval 9, DeltaF=-2.8271 +/- 0.2132, Sum=5.4976 +/- 0.1376 Interval 10, DeltaF=-1.0596 +/- 0.1528, Sum=4.8700 +/- 0.1383 Postopt. BAR free energy: 4.8700 +/- 0.1383 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 653 N_k = [300 353] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.49181937] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.86226026] relative max_delta = 2.818526e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0682 relative max_delta = 4.063651e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.9055 relative max_delta = 2.660561e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8625 relative max_delta = 6.258749e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8625 relative max_delta = 2.295843e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8625 relative max_delta = 2.795571e-13 Converged to tolerance of 2.795571e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8625 Final dimensionless free energies f_k = [ 0. 6.86251809] Computing normalized weights... Interval 1, DeltaF=6.8625 +/- 0.3149, Sum=4.0649 +/- 0.0587 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 814 N_k = [353 461] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.51572763] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.88034295] relative max_delta = 1.939089e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8941 relative max_delta = 7.261012e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 2.0180 relative max_delta = 6.141332e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 2.0188 relative max_delta = 3.752820e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 2.0188 relative max_delta = 1.651330e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 2.0188 relative max_delta = 1.759825e-15 Converged to tolerance of 1.759825e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 2.0188 Final dimensionless free energies f_k = [ 0. 2.01878757] Computing normalized weights... Interval 2, DeltaF=2.0188 +/- 0.2100, Sum=5.2607 +/- 0.0643 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 795 N_k = [461 334] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.59698838] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.40664931] relative max_delta = 3.364266e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4923 relative max_delta = 3.436502e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2503 relative max_delta = 2.332107e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2079 relative max_delta = 1.323072e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2078 relative max_delta = 3.174568e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2078 relative max_delta = 1.867007e-10 Converged to tolerance of 1.867007e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2078 Final dimensionless free energies f_k = [ 0. 3.20775813] Computing normalized weights... Interval 3, DeltaF=3.2078 +/- 0.2650, Sum=7.1608 +/- 0.0766 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 713 N_k = [334 379] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.9880742] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.73745553] relative max_delta = 4.313096e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9302 relative max_delta = 9.984719e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5815 relative max_delta = 4.610639e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3335 relative max_delta = 7.439040e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 1.703439e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 9.286677e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 2.794399e-13 Converged to tolerance of 2.794399e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3278 Final dimensionless free energies f_k = [ 0. 3.3278096] Computing normalized weights... Interval 4, DeltaF=3.3278 +/- 0.3025, Sum=9.1320 +/- 0.0938 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 790 N_k = [379 411] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.33501836] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.58847118] relative max_delta = 4.306971e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6594 relative max_delta = 1.075990e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2869 relative max_delta = 4.875889e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2448 relative max_delta = 3.378492e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2446 relative max_delta = 1.647667e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2446 relative max_delta = 3.905922e-09 Converged to tolerance of 3.905922e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2446 Final dimensionless free energies f_k = [ 0. 1.24464308] Computing normalized weights... Interval 5, DeltaF=1.2446 +/- 0.3262, Sum=9.8692 +/- 0.1130 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 734 N_k = [411 323] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.32717517] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.44237936] relative max_delta = 2.604194e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4491 relative max_delta = 1.502281e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5099 relative max_delta = 1.192310e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5103 relative max_delta = 6.425474e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5103 relative max_delta = 1.920912e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5103 relative max_delta = 5.874734e-15 Converged to tolerance of 5.874734e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5103 Final dimensionless free energies f_k = [ 0. -0.51025326] Computing normalized weights... Interval 6, DeltaF=-0.5103 +/- 0.2405, Sum=9.5670 +/- 0.1181 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 599 N_k = [323 276] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.06170741] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.44717941] relative max_delta = 2.663609e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4747 relative max_delta = 1.863999e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7227 relative max_delta = 1.439904e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7260 relative max_delta = 1.907059e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7260 relative max_delta = 3.946377e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7260 relative max_delta = 1.801041e-14 Converged to tolerance of 1.801041e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7260 Final dimensionless free energies f_k = [ 0. -1.72601493] Computing normalized weights... Interval 7, DeltaF=-1.7260 +/- 0.2687, Sum=8.5446 +/- 0.1256 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 593 N_k = [276 317] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.71526904] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.1417309] relative max_delta = 1.991202e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1604 relative max_delta = 8.632223e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3280 relative max_delta = 7.199976e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3272 relative max_delta = 3.410701e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3272 relative max_delta = 5.100112e-09 Converged to tolerance of 5.100112e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3272 Final dimensionless free energies f_k = [ 0. -2.3272011] Computing normalized weights... Interval 8, DeltaF=-2.3272 +/- 0.2344, Sum=7.1661 +/- 0.1298 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 630 N_k = [317 313] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.19226315] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.66833258] relative max_delta = 1.784146e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.6841 relative max_delta = 5.862934e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8256 relative max_delta = 5.008062e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8252 relative max_delta = 1.377169e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8252 relative max_delta = 4.488824e-10 Converged to tolerance of 4.488824e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8252 Final dimensionless free energies f_k = [ 0. -2.8251866] Computing normalized weights... Interval 9, DeltaF=-2.8252 +/- 0.2131, Sum=5.4927 +/- 0.1325 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 813 N_k = [313 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97811151] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.05203014] relative max_delta = 7.026284e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0527 relative max_delta = 6.377531e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0587 relative max_delta = 5.706190e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0587 relative max_delta = 3.545203e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0587 relative max_delta = 1.361748e-12 Converged to tolerance of 1.361748e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0587 Final dimensionless free energies f_k = [ 0. -1.05873914] Computing normalized weights... Interval 10, DeltaF=-1.0587 +/- 0.1475, Sum=4.8655 +/- 0.1331 Pairwise MBAR free energy: 4.8655 +/- 0.1331 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 3967 N_k = [300 353 461 334 379 411 323 276 317 313 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.07226169 2.17265354 1.94849689 1.67217772 1.83823117 1.91803736 1.91977841 1.77289727 1.08390698 0.68040478] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.09780684 3.5929394 3.52765301 3.09805923 3.36378939 3.44234432 3.35016573 2.96947457 1.79436944 1.20014204] relative max_delta = 4.395165e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3553 3.9796 4.4395 4.5956 4.9693 4.9962 4.7781 4.2183 2.8423 2.1970 relative max_delta = 3.213459e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8311 7.6418 12.2143 17.2285 18.5410 18.0893 16.6784 14.4462 11.3093 10.2173 relative max_delta = 7.319822e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8788 9.0107 12.2009 16.0619 17.2540 16.7241 15.0060 12.6890 9.8141 8.7549 relative max_delta = 1.018404e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8975 8.9013 12.1111 15.4697 16.6621 16.1279 14.4038 12.0792 9.2144 8.1554 relative max_delta = 3.659673e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8963 8.9021 12.1026 15.4296 16.6231 16.0889 14.3648 12.0402 9.1754 8.1164 relative max_delta = 2.413535e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8963 8.9021 12.1026 15.4294 16.6229 16.0887 14.3646 12.0400 9.1752 8.1162 relative max_delta = 1.116340e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8963 8.9021 12.1026 15.4294 16.6229 16.0887 14.3646 12.0400 9.1752 8.1162 relative max_delta = 2.419458e-10 Converged to tolerance of 2.419458e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8963 8.9021 12.1026 15.4294 16.6229 16.0887 14.3646 12.0400 9.1752 8.1162 Final dimensionless free energies f_k = [ 0. 6.89631194 8.90214038 12.10260088 15.42939263 16.62290597 16.0887496 14.36457891 12.0400241 9.17520259 8.11620998] Computing normalized weights... DeltaMij: [[ 0. 4.0849431 5.2730702 7.16882247 9.13940547 9.84636799 9.52996722 8.50867653 7.13175591 5.43481514 4.80753427] [-4.0849431 0. 1.18812709 3.08387937 5.05446236 5.76142488 5.44502412 4.42373343 3.04681281 1.34987204 0.72259117] [-5.2730702 -1.18812709 0. 1.89575227 3.86633527 4.57329779 4.25689702 3.23560634 1.85868571 0.16174494 -0.46553593] [-7.16882247 -3.08387937 -1.89575227 0. 1.97058299 2.67754552 2.36114475 1.33985406 -0.03706656 -1.73400733 -2.3612882 ] [-9.13940547 -5.05446236 -3.86633527 -1.97058299 0. 0.70696252 0.39056176 -0.63072893 -2.00764956 -3.70459033 -4.33187119] [-9.84636799 -5.76142488 -4.57329779 -2.67754552 -0.70696252 0. -0.31640077 -1.33769145 -2.71461208 -4.41155285 -5.03883372] [-9.52996722 -5.44502412 -4.25689702 -2.36114475 -0.39056176 0.31640077 0. -1.02129069 -2.39821131 -4.09515208 -4.72243295] [-8.50867653 -4.42373343 -3.23560634 -1.33985406 0.63072893 1.33769145 1.02129069 0. -1.37692062 -3.07386139 -3.70114226] [-7.13175591 -3.04681281 -1.85868571 0.03706656 2.00764956 2.71461208 2.39821131 1.37692062 0. -1.69694077 -2.32422164] [-5.43481514 -1.34987204 -0.16174494 1.73400733 3.70459033 4.41155285 4.09515208 3.07386139 1.69694077 0. -0.62728087] [-4.80753427 -0.72259117 0.46553593 2.3612882 4.33187119 5.03883372 4.72243295 3.70114226 2.32422164 0.62728087 0. ]] dDeltaMij: [[ 0. 0.05697342 0.07180577 0.08539061 0.10500714 0.12778152 0.13631525 0.14698851 0.15477785 0.15945286 0.16130115] [ 0.05697342 0. 0.0249219 0.05161392 0.08002734 0.10819554 0.11815245 0.13032182 0.13904796 0.14423373 0.14627445] [ 0.07180577 0.0249219 0. 0.03753721 0.07206212 0.10244669 0.11291166 0.12558988 0.1346231 0.13997289 0.14207483] [ 0.08539061 0.05161392 0.03753721 0. 0.05310082 0.09006443 0.10181109 0.11571196 0.12545844 0.13118251 0.13342301] [ 0.10500714 0.08002734 0.07206212 0.05310082 0. 0.06165383 0.07776721 0.0952476 0.10687669 0.11354146 0.11612282] [ 0.12778152 0.10819554 0.10244669 0.09006443 0.06165383 0. 0.03327191 0.06382512 0.08017722 0.08886516 0.09214034] [ 0.13631525 0.11815245 0.11291166 0.10181109 0.07776721 0.03327191 0. 0.04098252 0.06289415 0.07370968 0.07762825] [ 0.14698851 0.13032182 0.12558988 0.11571196 0.0952476 0.06382512 0.04098252 0. 0.03025979 0.04714336 0.05310223] [ 0.15477785 0.13904796 0.1346231 0.12545844 0.10687669 0.08017722 0.06289415 0.03025979 0. 0.02171817 0.03081228] [ 0.15945286 0.14423373 0.13997289 0.13118251 0.11354146 0.08886516 0.07370968 0.04714336 0.02171817 0. 0.01138026] [ 0.16130115 0.14627445 0.14207483 0.13342301 0.11612282 0.09214034 0.07762825 0.05310223 0.03081228 0.01138026 0. ]] Replica 28 / 40 Computing statistical inefficiencies: lambda 0: g = 1.680 lambda 1: g = 1.240 lambda 2: g = 1.536 lambda 3: g = 1.903 lambda 4: g = 1.190 lambda 5: g = 2.011 lambda 6: g = 1.803 lambda 7: g = 1.525 lambda 8: g = 2.251 lambda 9: g = 1.483 lambda 10: g = 1.000 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 438 313 500 500 476 282 178 308 500 327] Method: EXP Forward EXP: Interval 1, DeltaF=6.8629 +/- 0.4722, Sum=4.0652 +/- 0.1321 Interval 2, DeltaF=1.8816 +/- 0.2747, Sum=5.1797 +/- 0.1394 Interval 3, DeltaF=3.3564 +/- 0.3729, Sum=7.1679 +/- 0.1619 Interval 4, DeltaF=3.9516 +/- 0.4063, Sum=9.5085 +/- 0.1892 Interval 5, DeltaF=2.1478 +/- 0.4392, Sum=10.7807 +/- 0.2210 Interval 6, DeltaF=-0.5181 +/- 0.3707, Sum=10.4738 +/- 0.2355 Interval 7, DeltaF=-1.2675 +/- 0.3441, Sum=9.7230 +/- 0.2457 Interval 8, DeltaF=-2.4291 +/- 0.3553, Sum=8.2842 +/- 0.2569 Interval 9, DeltaF=-2.8887 +/- 0.2566, Sum=6.5731 +/- 0.2598 Interval 10, DeltaF=-1.0628 +/- 0.1701, Sum=5.9436 +/- 0.2604 Forward EXP free energy: 5.9436 +/- 0.2604 Reverse EXP: Interval 1, DeltaF=6.3807 +/- 0.4499, Sum=3.7795 +/- 0.1199 Interval 2, DeltaF=1.8973 +/- 0.3314, Sum=4.9033 +/- 0.1364 Interval 3, DeltaF=3.2963 +/- 0.3389, Sum=6.8559 +/- 0.1524 Interval 4, DeltaF=3.5063 +/- 0.3656, Sum=8.9328 +/- 0.1718 Interval 5, DeltaF=1.0741 +/- 0.4199, Sum=9.5691 +/- 0.2010 Interval 6, DeltaF=-0.3684 +/- 0.3235, Sum=9.3508 +/- 0.2104 Interval 7, DeltaF=-1.7734 +/- 0.4360, Sum=8.3004 +/- 0.2386 Interval 8, DeltaF=-2.4558 +/- 0.3309, Sum=6.8457 +/- 0.2473 Interval 9, DeltaF=-2.9015 +/- 0.2531, Sum=5.1271 +/- 0.2502 Interval 10, DeltaF=-1.1486 +/- 0.1826, Sum=4.4467 +/- 0.2509 Reverse EXP free energy: 4.4467 +/- 0.2509 Averge of forward and reverse EXP: Interval 1, DeltaF=6.6218 +/- 0.1639, Sum=3.9223 +/- 0.0159 Interval 2, DeltaF=1.8894 +/- 0.0725, Sum=5.0415 +/- 0.0162 Interval 3, DeltaF=3.3264 +/- 0.0981, Sum=7.0119 +/- 0.0172 Interval 4, DeltaF=3.7289 +/- 0.1156, Sum=9.2207 +/- 0.0189 Interval 5, DeltaF=1.6110 +/- 0.1422, Sum=10.1749 +/- 0.0224 Interval 6, DeltaF=-0.4433 +/- 0.0940, Sum=9.9123 +/- 0.0230 Interval 7, DeltaF=-1.5204 +/- 0.1219, Sum=9.0117 +/- 0.0246 Interval 8, DeltaF=-2.4425 +/- 0.0910, Sum=7.5650 +/- 0.0251 Interval 9, DeltaF=-2.8951 +/- 0.0500, Sum=5.8501 +/- 0.0252 Interval 10, DeltaF=-1.1057 +/- 0.0240, Sum=5.1952 +/- 0.0252 Average EXP free energy: 5.1952 +/- 0.0252 Interval 1, DeltaF=6.3807 +/- 0.1558, Sum=3.7795 +/- 0.0144 Interval 2, DeltaF=1.8816 +/- 0.2495, Sum=4.8941 +/- 0.0396 Interval 3, DeltaF=3.2963 +/- 0.2657, Sum=6.8466 +/- 0.0576 Interval 4, DeltaF=3.9516 +/- 0.3236, Sum=9.1873 +/- 0.0846 Interval 5, DeltaF=1.0741 +/- 0.3436, Sum=9.8235 +/- 0.1098 Interval 6, DeltaF=-0.5181 +/- 0.4196, Sum=9.5166 +/- 0.1514 Interval 7, DeltaF=-1.7734 +/- 0.4133, Sum=8.4662 +/- 0.1821 Interval 8, DeltaF=-2.4291 +/- 0.4619, Sum=7.0274 +/- 0.2217 Interval 9, DeltaF=-2.9015 +/- 0.4570, Sum=5.3087 +/- 0.2539 Interval 10, DeltaF=-1.0628 +/- 0.4779, Sum=4.6792 +/- 0.2877 Double-Wide EXP free energy: 4.6792 +/- 0.2877 Method: BAR Interval 1, DeltaF=6.8182 +/- 0.2993, Sum=4.0387 +/- 0.0531 Interval 2, DeltaF=1.9378 +/- 0.2077, Sum=5.1865 +/- 0.0589 Interval 3, DeltaF=3.2181 +/- 0.2582, Sum=7.0927 +/- 0.0709 Interval 4, DeltaF=3.5011 +/- 0.2763, Sum=9.1666 +/- 0.0841 Interval 5, DeltaF=1.3165 +/- 0.3053, Sum=9.9463 +/- 0.1006 Interval 6, DeltaF=-0.4877 +/- 0.2437, Sum=9.6575 +/- 0.1066 Interval 7, DeltaF=-1.6406 +/- 0.2938, Sum=8.6857 +/- 0.1182 Interval 8, DeltaF=-2.4142 +/- 0.2509, Sum=7.2556 +/- 0.1239 Interval 9, DeltaF=-2.8994 +/- 0.1988, Sum=5.5382 +/- 0.1261 Interval 10, DeltaF=-1.0726 +/- 0.1433, Sum=4.9028 +/- 0.1267 BAR free energy: 4.9028 +/- 0.1267 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8318 +/- 0.4795, Sum=4.0467 +/- 0.1362 Interval 2, DeltaF=1.9157 +/- 0.2998, Sum=5.1815 +/- 0.1462 Interval 3, DeltaF=3.1570 +/- 0.3041, Sum=7.0515 +/- 0.1562 Interval 4, DeltaF=3.4250 +/- 0.3700, Sum=9.0802 +/- 0.1760 Interval 5, DeltaF=1.3626 +/- 0.3386, Sum=9.8873 +/- 0.1886 Interval 6, DeltaF=-0.4776 +/- 0.2271, Sum=9.6045 +/- 0.1911 Interval 7, DeltaF=-1.7065 +/- 0.2673, Sum=8.5937 +/- 0.1957 Interval 8, DeltaF=-2.4463 +/- 0.3866, Sum=7.1446 +/- 0.2148 Interval 9, DeltaF=-2.8898 +/- 0.3838, Sum=5.4329 +/- 0.2318 Interval 10, DeltaF=-1.0938 +/- 0.1592, Sum=4.7850 +/- 0.2323 Unopt. BAR free energy: 4.7850 +/- 0.2323 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8153 +/- 0.2997, Sum=4.0370 +/- 0.0532 Interval 2, DeltaF=1.9379 +/- 0.2067, Sum=5.1849 +/- 0.0589 Interval 3, DeltaF=3.2099 +/- 0.2568, Sum=7.0862 +/- 0.0707 Interval 4, DeltaF=3.4861 +/- 0.2903, Sum=9.1512 +/- 0.0865 Interval 5, DeltaF=1.3289 +/- 0.3133, Sum=9.9384 +/- 0.1043 Interval 6, DeltaF=-0.4776 +/- 0.2271, Sum=9.6555 +/- 0.1087 Interval 7, DeltaF=-1.6276 +/- 0.3068, Sum=8.6914 +/- 0.1221 Interval 8, DeltaF=-2.4186 +/- 0.2665, Sum=7.2588 +/- 0.1292 Interval 9, DeltaF=-2.9003 +/- 0.1950, Sum=5.5408 +/- 0.1311 Interval 10, DeltaF=-1.0737 +/- 0.1376, Sum=4.9048 +/- 0.1316 Postopt. BAR free energy: 4.9048 +/- 0.1316 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 938 N_k = [500 438] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.53127986] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.85506679] relative max_delta = 2.726609e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0544 relative max_delta = 3.944357e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8356 relative max_delta = 2.605720e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8182 relative max_delta = 2.546597e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8182 relative max_delta = 3.572052e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8182 relative max_delta = 6.773787e-15 Converged to tolerance of 6.773787e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8182 Final dimensionless free energies f_k = [ 0. 6.81823553] Computing normalized weights... Interval 1, DeltaF=6.8182 +/- 0.2993, Sum=4.0387 +/- 0.0531 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 751 N_k = [438 313] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53297595] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.83778294] relative max_delta = 1.658558e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8478 relative max_delta = 5.438751e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9382 relative max_delta = 4.661371e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9378 relative max_delta = 2.084154e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9378 relative max_delta = 3.592851e-09 Converged to tolerance of 3.592851e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9378 Final dimensionless free energies f_k = [ 0. 1.93777467] Computing normalized weights... Interval 2, DeltaF=1.9378 +/- 0.2077, Sum=5.1865 +/- 0.0589 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 813 N_k = [313 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.62531592] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.44793626] relative max_delta = 3.360465e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5250 relative max_delta = 3.053683e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2174 relative max_delta = 2.152025e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2181 relative max_delta = 2.028306e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2181 relative max_delta = 3.786035e-09 Converged to tolerance of 3.786035e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2181 Final dimensionless free energies f_k = [ 0. 3.21809819] Computing normalized weights... Interval 3, DeltaF=3.2181 +/- 0.2582, Sum=7.0927 +/- 0.0709 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.02369556] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.80584264] relative max_delta = 4.331203e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0208 relative max_delta = 1.063935e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8410 relative max_delta = 4.738714e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.5126 relative max_delta = 9.350081e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.5011 relative max_delta = 3.262221e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.5011 relative max_delta = 4.183618e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.5011 relative max_delta = 6.889564e-12 Converged to tolerance of 6.889564e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.5011 Final dimensionless free energies f_k = [ 0. 3.50111428] Computing normalized weights... Interval 4, DeltaF=3.5011 +/- 0.2763, Sum=9.1666 +/- 0.0841 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 976 N_k = [500 476] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.37056499] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.64608209] relative max_delta = 4.264429e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7185 relative max_delta = 1.008375e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3593 relative max_delta = 4.713818e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3167 relative max_delta = 3.235732e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3165 relative max_delta = 1.538391e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3165 relative max_delta = 3.466332e-09 Converged to tolerance of 3.466332e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3165 Final dimensionless free energies f_k = [ 0. 1.31646876] Computing normalized weights... Interval 5, DeltaF=1.3165 +/- 0.3053, Sum=9.9463 +/- 0.1006 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 758 N_k = [476 282] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.30654597] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.41887485] relative max_delta = 2.681681e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4257 relative max_delta = 1.603318e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4872 relative max_delta = 1.262828e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4877 relative max_delta = 9.017770e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4877 relative max_delta = 4.661820e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4877 relative max_delta = 3.187231e-15 Converged to tolerance of 3.187231e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4877 Final dimensionless free energies f_k = [ 0. -0.48766856] Computing normalized weights... Interval 6, DeltaF=-0.4877 +/- 0.2437, Sum=9.6575 +/- 0.1066 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 460 N_k = [282 178] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98050777] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35563295] relative max_delta = 2.767159e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3834 relative max_delta = 2.006400e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6345 relative max_delta = 1.536280e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6406 relative max_delta = 3.743963e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6406 relative max_delta = 2.393591e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6406 relative max_delta = 9.791868e-13 Converged to tolerance of 9.791868e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6406 Final dimensionless free energies f_k = [ 0. -1.64063964] Computing normalized weights... Interval 7, DeltaF=-1.6406 +/- 0.2938, Sum=8.6857 +/- 0.1182 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 486 N_k = [178 308] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.80685338] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.23118089] relative max_delta = 1.901807e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2498 relative max_delta = 8.273023e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.4167 relative max_delta = 6.905674e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.4142 relative max_delta = 1.018127e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.4142 relative max_delta = 2.032476e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.4142 relative max_delta = 8.461564e-15 Converged to tolerance of 8.461564e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.4142 Final dimensionless free energies f_k = [ 0. -2.41422317] Computing normalized weights... Interval 8, DeltaF=-2.4142 +/- 0.2509, Sum=7.2556 +/- 0.1239 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 808 N_k = [308 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34603668] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.77363038] relative max_delta = 1.541639e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7864 relative max_delta = 4.572639e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9007 relative max_delta = 3.942000e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8994 relative max_delta = 4.430139e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8994 relative max_delta = 5.159325e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8994 relative max_delta = 6.126566e-16 Converged to tolerance of 6.126566e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8994 Final dimensionless free energies f_k = [ 0. -2.8994331] Computing normalized weights... Interval 9, DeltaF=-2.8994 +/- 0.1988, Sum=5.5382 +/- 0.1261 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 827 N_k = [500 327] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98401732] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06573074] relative max_delta = 7.667361e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0664 relative max_delta = 6.453462e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 5.775285e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 3.059438e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 8.651033e-13 Converged to tolerance of 8.651033e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0726 Final dimensionless free energies f_k = [ 0. -1.07261688] Computing normalized weights... Interval 10, DeltaF=-1.0726 +/- 0.1433, Sum=4.9028 +/- 0.1267 Pairwise MBAR free energy: 4.9028 +/- 0.1267 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4322 N_k = [500 438 313 500 500 476 282 178 308 500 327] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89331943 1.79710451 1.66088663 1.41265729 1.56810903 1.64388257 1.70736555 1.67216446 0.85441006 0.28730831] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.80042668 3.02838578 3.0256005 2.65394018 2.90678361 2.99501902 2.99591866 2.7397828 1.37367045 0.6266693 ] relative max_delta = 4.506407e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0859 3.4557 3.9075 4.1515 4.5351 4.5757 4.4641 4.0248 2.4647 1.6834 relative max_delta = 3.558698e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8131 7.5067 11.6083 16.9542 18.4697 18.0645 16.8711 14.6877 11.4441 10.3614 relative max_delta = 7.544558e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7960 8.8725 12.0778 15.9535 17.3176 16.8255 15.1627 12.7898 9.8428 8.7694 relative max_delta = 1.095927e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8047 8.7428 11.9705 15.4584 16.8194 16.3180 14.6338 12.2456 9.3146 8.2423 relative max_delta = 3.235422e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8037 8.7426 11.9662 15.4329 16.7945 16.2931 14.6089 12.2207 9.2897 8.2174 relative max_delta = 1.515255e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8037 8.7426 11.9662 15.4329 16.7945 16.2931 14.6088 12.2206 9.2896 8.2173 relative max_delta = 4.674326e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8037 8.7426 11.9662 15.4329 16.7945 16.2931 14.6088 12.2206 9.2896 8.2173 relative max_delta = 4.576653e-11 Converged to tolerance of 4.576653e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8037 8.7426 11.9662 15.4329 16.7945 16.2931 14.6088 12.2206 9.2896 8.2173 Final dimensionless free energies f_k = [ 0. 6.8037169 8.74264595 11.96616732 15.43285246 16.79446439 16.29306293 14.60879154 12.22058874 9.28964283 8.21728847] Computing normalized weights... DeltaMij: [[ 0. 4.0300956 5.17859569 7.08800778 9.14145485 9.94798845 9.65098964 8.65333279 7.23871109 5.50260237 4.86740683] [-4.0300956 0. 1.14850009 3.05791217 5.11135925 5.91789285 5.62089404 4.62323719 3.20861548 1.47250677 0.83731123] [-5.17859569 -1.14850009 0. 1.90941209 3.96285916 4.76939276 4.47239395 3.47473711 2.0601154 0.32400668 -0.31118885] [-7.08800778 -3.05791217 -1.90941209 0. 2.05344708 2.85998067 2.56298186 1.56532502 0.15070331 -1.58540541 -2.22060094] [-9.14145485 -5.11135925 -3.96285916 -2.05344708 0. 0.8065336 0.50953479 -0.48812206 -1.90274376 -3.63885248 -4.27404802] [-9.94798845 -5.91789285 -4.76939276 -2.85998067 -0.8065336 0. -0.29699881 -1.29465565 -2.70927736 -4.44538608 -5.08058162] [-9.65098964 -5.62089404 -4.47239395 -2.56298186 -0.50953479 0.29699881 0. -0.99765684 -2.41227855 -4.14838727 -4.78358281] [-8.65333279 -4.62323719 -3.47473711 -1.56532502 0.48812206 1.29465565 0.99765684 0. -1.41462171 -3.15073042 -3.78592596] [-7.23871109 -3.20861548 -2.0601154 -0.15070331 1.90274376 2.70927736 2.41227855 1.41462171 0. -1.73610872 -2.37130425] [-5.50260237 -1.47250677 -0.32400668 1.58540541 3.63885248 4.44538608 4.14838727 3.15073042 1.73610872 0. -0.63519554] [-4.86740683 -0.83731123 0.31118885 2.22060094 4.27404802 5.08058162 4.78358281 3.78592596 2.37130425 0.63519554 0. ]] dDeltaMij: [[ 0. 0.05246938 0.06613543 0.0797605 0.09452272 0.11344723 0.12276301 0.13714907 0.1483836 0.15342947 0.15517463] [ 0.05246938 0. 0.02371349 0.04939756 0.07084069 0.09462693 0.10561599 0.12204035 0.13454246 0.14008777 0.14199699] [ 0.06613543 0.02371349 0. 0.03490892 0.06194338 0.08816513 0.09986774 0.11710114 0.13007883 0.13580653 0.13777509] [ 0.0797605 0.04939756 0.03490892 0. 0.04432629 0.076771 0.08996885 0.10878186 0.12264305 0.12870209 0.13077764] [ 0.09452272 0.07084069 0.06194338 0.04432629 0. 0.05287379 0.07064198 0.09343436 0.10926007 0.11602015 0.11831837] [ 0.11344723 0.09462693 0.08816513 0.076771 0.05287379 0. 0.03440433 0.06977538 0.08989497 0.09799861 0.10070886] [ 0.12276301 0.10561599 0.09986774 0.08996885 0.07064198 0.03440433 0. 0.04712543 0.07297481 0.08280197 0.08599351] [ 0.13714907 0.12204035 0.11710114 0.10878186 0.09343436 0.06977538 0.04712543 0. 0.03424323 0.04987221 0.05506475] [ 0.1483836 0.13454246 0.13007883 0.12264305 0.10926007 0.08989497 0.07297481 0.03424323 0. 0.02096602 0.02961428] [ 0.15342947 0.14008777 0.13580653 0.12870209 0.11602015 0.09799861 0.08280197 0.04987221 0.02096602 0. 0.01099965] [ 0.15517463 0.14199699 0.13777509 0.13077764 0.11831837 0.10070886 0.08599351 0.05506475 0.02961428 0.01099965 0. ]] Replica 29 / 40 Computing statistical inefficiencies: lambda 0: g = 1.743 lambda 1: g = 1.964 lambda 2: g = 1.372 lambda 3: g = 2.103 lambda 4: g = 1.116 lambda 5: g = 2.307 lambda 6: g = 2.227 lambda 7: g = 1.667 lambda 8: g = 1.068 lambda 9: g = 1.900 lambda 10: g = 2.166 Subsampling data to produce uncorrelated samples... number of samples per lambda: [476 327 418 463 500 500 500 251 209 447 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.8663 +/- 0.3829, Sum=4.0672 +/- 0.0868 Interval 2, DeltaF=2.0558 +/- 0.2733, Sum=5.2849 +/- 0.0975 Interval 3, DeltaF=2.5834 +/- 0.7561, Sum=6.8152 +/- 0.3524 Interval 4, DeltaF=4.0909 +/- 0.5067, Sum=9.2384 +/- 0.3838 Interval 5, DeltaF=1.3343 +/- 0.7835, Sum=10.0287 +/- 0.5287 Interval 6, DeltaF=-0.3709 +/- 0.3209, Sum=9.8090 +/- 0.5322 Interval 7, DeltaF=-1.6975 +/- 0.3952, Sum=8.8036 +/- 0.5402 Interval 8, DeltaF=-2.2817 +/- 0.3593, Sum=7.4520 +/- 0.5456 Interval 9, DeltaF=-2.9633 +/- 0.3171, Sum=5.6967 +/- 0.5488 Interval 10, DeltaF=-1.0754 +/- 0.1702, Sum=5.0598 +/- 0.5491 Forward EXP free energy: 5.0598 +/- 0.5491 Reverse EXP: Interval 1, DeltaF=6.6806 +/- 0.4580, Sum=3.9572 +/- 0.1243 Interval 2, DeltaF=1.8203 +/- 0.2434, Sum=5.0354 +/- 0.1291 Interval 3, DeltaF=3.2674 +/- 0.3184, Sum=6.9709 +/- 0.1424 Interval 4, DeltaF=3.5462 +/- 0.3765, Sum=9.0714 +/- 0.1653 Interval 5, DeltaF=1.2010 +/- 0.4003, Sum=9.7828 +/- 0.1906 Interval 6, DeltaF=-0.7276 +/- 0.2748, Sum=9.3518 +/- 0.1958 Interval 7, DeltaF=-1.3601 +/- 0.3772, Sum=8.5462 +/- 0.2132 Interval 8, DeltaF=-2.2253 +/- 0.3550, Sum=7.2280 +/- 0.2259 Interval 9, DeltaF=-2.7089 +/- 0.3674, Sum=5.6234 +/- 0.2396 Interval 10, DeltaF=-1.0504 +/- 0.2131, Sum=5.0012 +/- 0.2411 Reverse EXP free energy: 5.0012 +/- 0.2411 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7735 +/- 0.1393, Sum=4.0122 +/- 0.0115 Interval 2, DeltaF=1.9381 +/- 0.0519, Sum=5.1602 +/- 0.0116 Interval 3, DeltaF=2.9254 +/- 0.3160, Sum=6.8930 +/- 0.0603 Interval 4, DeltaF=3.8185 +/- 0.1596, Sum=9.1549 +/- 0.0621 Interval 5, DeltaF=1.2677 +/- 0.3452, Sum=9.9058 +/- 0.0940 Interval 6, DeltaF=-0.5492 +/- 0.0695, Sum=9.5804 +/- 0.0941 Interval 7, DeltaF=-1.5288 +/- 0.1150, Sum=8.6749 +/- 0.0944 Interval 8, DeltaF=-2.2535 +/- 0.0982, Sum=7.3400 +/- 0.0946 Interval 9, DeltaF=-2.8361 +/- 0.0916, Sum=5.6601 +/- 0.0947 Interval 10, DeltaF=-1.0629 +/- 0.0293, Sum=5.0305 +/- 0.0947 Average EXP free energy: 5.0305 +/- 0.0947 Interval 1, DeltaF=6.6806 +/- 0.1615, Sum=3.9572 +/- 0.0154 Interval 2, DeltaF=2.0558 +/- 0.1696, Sum=5.1749 +/- 0.0230 Interval 3, DeltaF=3.2674 +/- 0.2498, Sum=7.1104 +/- 0.0435 Interval 4, DeltaF=4.0909 +/- 0.6770, Sum=9.5336 +/- 0.2750 Interval 5, DeltaF=1.2010 +/- 0.3279, Sum=10.2450 +/- 0.2822 Interval 6, DeltaF=-0.3709 +/- 0.9747, Sum=10.0253 +/- 0.6295 Interval 7, DeltaF=-1.3601 +/- 0.3761, Sum=9.2196 +/- 0.6351 Interval 8, DeltaF=-2.2817 +/- 0.9975, Sum=7.8681 +/- 0.8665 Interval 9, DeltaF=-2.7089 +/- 0.4278, Sum=6.2635 +/- 0.8732 Interval 10, DeltaF=-1.0754 +/- 1.0087, Sum=5.6265 +/- 1.0610 Double-Wide EXP free energy: 5.6265 +/- 1.0610 Method: BAR Interval 1, DeltaF=6.7338 +/- 0.3048, Sum=3.9887 +/- 0.0550 Interval 2, DeltaF=1.9921 +/- 0.2082, Sum=5.1687 +/- 0.0607 Interval 3, DeltaF=3.3876 +/- 0.2481, Sum=7.1753 +/- 0.0708 Interval 4, DeltaF=3.5642 +/- 0.2792, Sum=9.2865 +/- 0.0846 Interval 5, DeltaF=1.3179 +/- 0.3060, Sum=10.0671 +/- 0.1011 Interval 6, DeltaF=-0.6186 +/- 0.2234, Sum=9.7007 +/- 0.1053 Interval 7, DeltaF=-1.6412 +/- 0.2581, Sum=8.7286 +/- 0.1125 Interval 8, DeltaF=-2.2525 +/- 0.2566, Sum=7.3943 +/- 0.1191 Interval 9, DeltaF=-2.8761 +/- 0.2215, Sum=5.6907 +/- 0.1226 Interval 10, DeltaF=-1.0768 +/- 0.1413, Sum=5.0529 +/- 0.1231 BAR free energy: 5.0529 +/- 0.1231 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8389 +/- 0.5573, Sum=4.0509 +/- 0.1840 Interval 2, DeltaF=2.0299 +/- 0.2553, Sum=5.2534 +/- 0.1880 Interval 3, DeltaF=3.2665 +/- 0.3328, Sum=7.1882 +/- 0.1991 Interval 4, DeltaF=3.6734 +/- 0.3675, Sum=9.3641 +/- 0.2146 Interval 5, DeltaF=1.2979 +/- 0.3437, Sum=10.1330 +/- 0.2257 Interval 6, DeltaF=-0.6403 +/- 0.2186, Sum=9.7537 +/- 0.2275 Interval 7, DeltaF=-1.5852 +/- 0.2162, Sum=8.8147 +/- 0.2291 Interval 8, DeltaF=-2.2238 +/- 0.3109, Sum=7.4975 +/- 0.2362 Interval 9, DeltaF=-2.7858 +/- 0.4259, Sum=5.8474 +/- 0.2595 Interval 10, DeltaF=-1.0740 +/- 0.2085, Sum=5.2112 +/- 0.2607 Unopt. BAR free energy: 5.2112 +/- 0.2607 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7485 +/- 0.3040, Sum=3.9974 +/- 0.0548 Interval 2, DeltaF=1.9919 +/- 0.2084, Sum=5.1773 +/- 0.0605 Interval 3, DeltaF=3.3901 +/- 0.2514, Sum=7.1853 +/- 0.0711 Interval 4, DeltaF=3.5458 +/- 0.2692, Sum=9.2856 +/- 0.0831 Interval 5, DeltaF=1.3133 +/- 0.3149, Sum=10.0635 +/- 0.1018 Interval 6, DeltaF=-0.6046 +/- 0.2304, Sum=9.7053 +/- 0.1065 Interval 7, DeltaF=-1.6476 +/- 0.2729, Sum=8.7294 +/- 0.1153 Interval 8, DeltaF=-2.2499 +/- 0.2551, Sum=7.3967 +/- 0.1216 Interval 9, DeltaF=-2.8786 +/- 0.2142, Sum=5.6916 +/- 0.1246 Interval 10, DeltaF=-1.0767 +/- 0.1436, Sum=5.0538 +/- 0.1252 Postopt. BAR free energy: 5.0538 +/- 0.1252 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 803 N_k = [476 327] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.83888063] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 5.08054112] relative max_delta = 2.443953e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.2537 relative max_delta = 3.295615e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7898 relative max_delta = 2.262335e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7339 relative max_delta = 8.301044e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7338 relative max_delta = 5.705958e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7338 relative max_delta = 2.735438e-12 Converged to tolerance of 2.735438e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7338 Final dimensionless free energies f_k = [ 0. 6.73381533] Computing normalized weights... Interval 1, DeltaF=6.7338 +/- 0.3048, Sum=3.9887 +/- 0.0550 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 745 N_k = [327 418] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.54413895] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.8790129] relative max_delta = 1.782180e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8903 relative max_delta = 5.951980e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9916 relative max_delta = 5.089253e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9921 relative max_delta = 2.427755e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9921 relative max_delta = 6.415279e-09 Converged to tolerance of 6.415279e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9921 Final dimensionless free energies f_k = [ 0. 1.99210606] Computing normalized weights... Interval 2, DeltaF=1.9921 +/- 0.2082, Sum=5.1687 +/- 0.0607 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 881 N_k = [418 463] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.70933643] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.58326283] relative max_delta = 3.383033e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6672 relative max_delta = 3.145919e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.4135 relative max_delta = 2.186472e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3876 relative max_delta = 7.656933e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3876 relative max_delta = 3.311834e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3876 relative max_delta = 6.611041e-13 Converged to tolerance of 6.611041e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3876 Final dimensionless free energies f_k = [ 0. 3.38757836] Computing normalized weights... Interval 3, DeltaF=3.3876 +/- 0.2481, Sum=7.1753 +/- 0.0708 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 963 N_k = [463 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.06204799] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.86272862] relative max_delta = 4.298429e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0723 relative max_delta = 1.011248e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8636 relative max_delta = 4.636319e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.5727 relative max_delta = 8.140570e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.5642 relative max_delta = 2.390282e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.5642 relative max_delta = 2.142851e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.5642 relative max_delta = 1.723931e-12 Converged to tolerance of 1.723931e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.5642 Final dimensionless free energies f_k = [ 0. 3.56418976] Computing normalized weights... Interval 4, DeltaF=3.5642 +/- 0.2792, Sum=9.2865 +/- 0.0846 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.35371175] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.62292115] relative max_delta = 4.321725e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6991 relative max_delta = 1.089915e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3705 relative max_delta = 4.898829e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3183 relative max_delta = 3.963775e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3179 relative max_delta = 2.581205e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3179 relative max_delta = 1.090957e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3179 relative max_delta = 5.054455e-16 Converged to tolerance of 5.054455e-16 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3179 Final dimensionless free energies f_k = [ 0. 1.31791435] Computing normalized weights... Interval 5, DeltaF=1.3179 +/- 0.3060, Sum=10.0671 +/- 0.1011 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.39479832] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.53442194] relative max_delta = 2.612610e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.5428 relative max_delta = 1.544656e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.6183 relative max_delta = 1.221383e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.6186 relative max_delta = 4.444298e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.6186 relative max_delta = 6.320568e-09 Converged to tolerance of 6.320568e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.6186 Final dimensionless free energies f_k = [ 0. -0.61860288] Computing normalized weights... Interval 6, DeltaF=-0.6186 +/- 0.2234, Sum=9.7007 +/- 0.1053 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 751 N_k = [500 251] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01347681] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.38300982] relative max_delta = 2.671948e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4080 relative max_delta = 1.776817e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6346 relative max_delta = 1.386123e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6412 relative max_delta = 4.015988e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6412 relative max_delta = 3.493690e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6412 relative max_delta = 2.646756e-12 Converged to tolerance of 2.646756e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6412 Final dimensionless free energies f_k = [ 0. -1.64120098] Computing normalized weights... Interval 7, DeltaF=-1.6412 +/- 0.2581, Sum=8.7286 +/- 0.1125 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 460 N_k = [251 209] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.56239802] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.02477129] relative max_delta = 2.283583e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0475 relative max_delta = 1.108817e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2519 relative max_delta = 9.076980e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2525 relative max_delta = 2.706677e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2525 relative max_delta = 4.257891e-09 Converged to tolerance of 4.257891e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2525 Final dimensionless free energies f_k = [ 0. -2.2524861] Computing normalized weights... Interval 8, DeltaF=-2.2525 +/- 0.2566, Sum=7.3943 +/- 0.1191 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 656 N_k = [209 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.24407915] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.71558483] relative max_delta = 1.736295e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7320 relative max_delta = 6.018141e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8792 relative max_delta = 5.112426e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8761 relative max_delta = 1.071065e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8761 relative max_delta = 4.515555e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8761 relative max_delta = 8.137113e-14 Converged to tolerance of 8.137113e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8761 Final dimensionless free energies f_k = [ 0. -2.87614295] Computing normalized weights... Interval 9, DeltaF=-2.8761 +/- 0.2215, Sum=5.6907 +/- 0.1226 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 947 N_k = [447 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9842433] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06881644] relative max_delta = 7.912784e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0696 relative max_delta = 7.474771e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0768 relative max_delta = 6.681987e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0768 relative max_delta = 1.488176e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0768 relative max_delta = 6.949142e-14 Converged to tolerance of 6.949142e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0768 Final dimensionless free energies f_k = [ 0. -1.07680959] Computing normalized weights... Interval 10, DeltaF=-1.0768 +/- 0.1413, Sum=5.0529 +/- 0.1231 Pairwise MBAR free energy: 5.0529 +/- 0.1231 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4591 N_k = [476 327 418 463 500 500 500 251 209 447 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89870864 1.87960875 1.65927958 1.48312915 1.60881867 1.54742516 1.458414 1.39185507 0.9151851 0.47235181] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.7634368 3.08997274 3.03705052 2.76913106 2.92272354 2.8089393 2.60885486 2.37477533 1.49138497 0.87148209] relative max_delta = 4.458845e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0231 3.4835 3.9533 4.2796 4.5669 4.4071 4.1045 3.7290 2.6299 1.9568 relative max_delta = 3.600190e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5328 7.2287 11.8340 16.9926 18.4359 17.8617 16.5929 14.8284 11.7452 10.6057 relative max_delta = 7.522823e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6758 8.8292 12.0989 16.0702 17.3524 16.7654 15.1770 12.9809 10.0715 8.9872 relative max_delta = 1.064741e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6878 8.6578 12.0514 15.6000 16.8782 16.2876 14.6849 12.4553 9.5742 8.4884 relative max_delta = 3.113934e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6856 8.6571 12.0446 15.5759 16.8548 16.2642 14.6615 12.4316 9.5508 8.4650 relative max_delta = 1.427299e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6856 8.6571 12.0446 15.5759 16.8547 16.2641 14.6615 12.4315 9.5507 8.4649 relative max_delta = 3.483519e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6856 8.6571 12.0446 15.5759 16.8547 16.2641 14.6615 12.4315 9.5507 8.4649 relative max_delta = 2.426393e-11 Converged to tolerance of 2.426393e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6856 8.6571 12.0446 15.5759 16.8547 16.2641 14.6615 12.4315 9.5507 8.4649 Final dimensionless free energies f_k = [ 0. 6.68560554 8.65708528 12.0445506 15.57587081 16.85471898 16.26412626 14.66145655 12.43150539 9.55070034 8.46493483] Computing normalized weights... DeltaMij: [[ 0. 3.96013384 5.12791491 7.13443712 9.22616996 9.98367949 9.63384937 8.68452825 7.3636449 5.65723648 5.01409702] [-3.96013384 0. 1.16778107 3.17430329 5.26603612 6.02354565 5.67371553 4.72439441 3.40351106 1.69710264 1.05396318] [-5.12791491 -1.16778107 0. 2.00652221 4.09825505 4.85576458 4.50593446 3.55661334 2.23572999 0.52932157 -0.11381789] [-7.13443712 -3.17430329 -2.00652221 0. 2.09173284 2.84924237 2.49941225 1.55009113 0.22920778 -1.47720064 -2.1203401 ] [-9.22616996 -5.26603612 -4.09825505 -2.09173284 0. 0.75750953 0.40767941 -0.54164171 -1.86252506 -3.56893348 -4.21207294] [-9.98367949 -6.02354565 -4.85576458 -2.84924237 -0.75750953 0. -0.34983012 -1.29915124 -2.62003459 -4.32644301 -4.96958247] [-9.63384937 -5.67371553 -4.50593446 -2.49941225 -0.40767941 0.34983012 0. -0.94932112 -2.27020447 -3.97661289 -4.61975235] [-8.68452825 -4.72439441 -3.55661334 -1.55009113 0.54164171 1.29915124 0.94932112 0. -1.32088335 -3.02729177 -3.67043123] [-7.3636449 -3.40351106 -2.23572999 -0.22920778 1.86252506 2.62003459 2.27020447 1.32088335 0. -1.70640842 -2.34954788] [-5.65723648 -1.69710264 -0.52932157 1.47720064 3.56893348 4.32644301 3.97661289 3.02729177 1.70640842 0. -0.64313946] [-5.01409702 -1.05396318 0.11381789 2.1203401 4.21207294 4.96958247 4.61975235 3.67043123 2.34954788 0.64313946 0. ]] dDeltaMij: [[ 0. 0.05396254 0.06839658 0.08071459 0.09578956 0.11509361 0.12239308 0.13128362 0.14110623 0.14747421 0.14946129] [ 0.05396254 0. 0.02376922 0.04770745 0.07036169 0.09498566 0.10371013 0.11406627 0.12524653 0.13237964 0.13458976] [ 0.06839658 0.02376922 0. 0.03340243 0.06190541 0.08890554 0.09817181 0.10905516 0.12070048 0.12808701 0.13036992] [ 0.08071459 0.04770745 0.03340243 0. 0.04504068 0.07805172 0.08846312 0.10040437 0.11294519 0.12080684 0.12322469] [ 0.09578956 0.07036169 0.06190541 0.04504068 0. 0.05418171 0.06828897 0.08318121 0.09795231 0.1069221 0.10964656] [ 0.11509361 0.09498566 0.08890554 0.07805172 0.05418171 0. 0.0283581 0.05494241 0.07548793 0.08680837 0.09014266] [ 0.12239308 0.10371013 0.09817181 0.08846312 0.06828897 0.0283581 0. 0.03663924 0.06291195 0.07617625 0.07995681] [ 0.13128362 0.11406627 0.10905516 0.10040437 0.08318121 0.05494241 0.03663924 0. 0.03390342 0.05266325 0.05801311] [ 0.14110623 0.12524653 0.12070048 0.11294519 0.09795231 0.07548793 0.06291195 0.03390342 0. 0.02369556 0.03196425] [ 0.14747421 0.13237964 0.12808701 0.12080684 0.1069221 0.08680837 0.07617625 0.05266325 0.02369556 0. 0.01072657] [ 0.14946129 0.13458976 0.13036992 0.12322469 0.10964656 0.09014266 0.07995681 0.05801311 0.03196425 0.01072657 0. ]] Replica 30 / 40 Computing statistical inefficiencies: lambda 0: g = 1.937 lambda 1: g = 1.307 lambda 2: g = 1.280 lambda 3: g = 1.214 lambda 4: g = 2.302 lambda 5: g = 1.351 lambda 6: g = 1.090 lambda 7: g = 1.438 lambda 8: g = 1.878 lambda 9: g = 1.580 lambda 10: g = 2.227 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 477 417 337 500 371 243 217 333 412] Method: EXP Forward EXP: Interval 1, DeltaF=6.8395 +/- 0.4862, Sum=4.0513 +/- 0.1400 Interval 2, DeltaF=1.8070 +/- 0.2709, Sum=5.1217 +/- 0.1466 Interval 3, DeltaF=2.9744 +/- 0.5523, Sum=6.8835 +/- 0.2327 Interval 4, DeltaF=3.8750 +/- 0.4550, Sum=9.1788 +/- 0.2630 Interval 5, DeltaF=2.5154 +/- 0.3776, Sum=10.6688 +/- 0.2762 Interval 6, DeltaF=-0.3566 +/- 0.3256, Sum=10.4576 +/- 0.2833 Interval 7, DeltaF=-1.4093 +/- 0.3243, Sum=9.6228 +/- 0.2901 Interval 8, DeltaF=-2.3803 +/- 0.3514, Sum=8.2128 +/- 0.2991 Interval 9, DeltaF=-2.8249 +/- 0.2710, Sum=6.5395 +/- 0.3023 Interval 10, DeltaF=-1.0253 +/- 0.1754, Sum=5.9322 +/- 0.3028 Forward EXP free energy: 5.9322 +/- 0.3028 Reverse EXP: Interval 1, DeltaF=6.7643 +/- 0.4901, Sum=4.0067 +/- 0.1423 Interval 2, DeltaF=1.8322 +/- 0.2785, Sum=5.0920 +/- 0.1495 Interval 3, DeltaF=3.1240 +/- 0.3800, Sum=6.9425 +/- 0.1722 Interval 4, DeltaF=3.3044 +/- 0.3742, Sum=8.8998 +/- 0.1912 Interval 5, DeltaF=1.0880 +/- 0.4029, Sum=9.5442 +/- 0.2140 Interval 6, DeltaF=-0.5499 +/- 0.2905, Sum=9.2185 +/- 0.2198 Interval 7, DeltaF=-1.7149 +/- 0.3187, Sum=8.2027 +/- 0.2278 Interval 8, DeltaF=-2.5181 +/- 0.3303, Sum=6.7112 +/- 0.2368 Interval 9, DeltaF=-2.9274 +/- 0.2777, Sum=4.9772 +/- 0.2412 Interval 10, DeltaF=-1.0888 +/- 0.1797, Sum=4.3322 +/- 0.2420 Reverse EXP free energy: 4.3322 +/- 0.2420 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8019 +/- 0.1834, Sum=4.0290 +/- 0.0199 Interval 2, DeltaF=1.8196 +/- 0.0581, Sum=5.1068 +/- 0.0200 Interval 3, DeltaF=3.0492 +/- 0.1837, Sum=6.9130 +/- 0.0283 Interval 4, DeltaF=3.5897 +/- 0.1360, Sum=9.0393 +/- 0.0303 Interval 5, DeltaF=1.8017 +/- 0.1176, Sum=10.1065 +/- 0.0314 Interval 6, DeltaF=-0.4532 +/- 0.0737, Sum=9.8380 +/- 0.0316 Interval 7, DeltaF=-1.5621 +/- 0.0796, Sum=8.9128 +/- 0.0318 Interval 8, DeltaF=-2.4492 +/- 0.0897, Sum=7.4620 +/- 0.0322 Interval 9, DeltaF=-2.8761 +/- 0.0580, Sum=5.7584 +/- 0.0322 Interval 10, DeltaF=-1.0571 +/- 0.0243, Sum=5.1322 +/- 0.0322 Average EXP free energy: 5.1322 +/- 0.0322 Interval 1, DeltaF=6.7643 +/- 0.1849, Sum=4.0067 +/- 0.0202 Interval 2, DeltaF=1.8070 +/- 0.2634, Sum=5.0771 +/- 0.0458 Interval 3, DeltaF=3.1240 +/- 0.2964, Sum=6.9276 +/- 0.0693 Interval 4, DeltaF=3.8750 +/- 0.4563, Sum=9.2229 +/- 0.1415 Interval 5, DeltaF=1.0880 +/- 0.3729, Sum=9.8673 +/- 0.1637 Interval 6, DeltaF=-0.3566 +/- 0.5141, Sum=9.6561 +/- 0.2265 Interval 7, DeltaF=-1.7149 +/- 0.4113, Sum=8.6403 +/- 0.2477 Interval 8, DeltaF=-2.3803 +/- 0.5414, Sum=7.2303 +/- 0.3025 Interval 9, DeltaF=-2.9274 +/- 0.4392, Sum=5.4964 +/- 0.3233 Interval 10, DeltaF=-1.0253 +/- 0.5560, Sum=4.8890 +/- 0.3716 Double-Wide EXP free energy: 4.8890 +/- 0.3716 Method: BAR Interval 1, DeltaF=6.8415 +/- 0.2993, Sum=4.0525 +/- 0.0530 Interval 2, DeltaF=1.8734 +/- 0.1945, Sum=5.1622 +/- 0.0576 Interval 3, DeltaF=3.1674 +/- 0.2503, Sum=7.0383 +/- 0.0685 Interval 4, DeltaF=3.4987 +/- 0.2970, Sum=9.1107 +/- 0.0861 Interval 5, DeltaF=1.2324 +/- 0.3292, Sum=9.8407 +/- 0.1074 Interval 6, DeltaF=-0.5620 +/- 0.2298, Sum=9.5078 +/- 0.1119 Interval 7, DeltaF=-1.6228 +/- 0.2701, Sum=8.5466 +/- 0.1199 Interval 8, DeltaF=-2.3641 +/- 0.2565, Sum=7.1462 +/- 0.1261 Interval 9, DeltaF=-2.9066 +/- 0.2167, Sum=5.4245 +/- 0.1292 Interval 10, DeltaF=-1.0634 +/- 0.1469, Sum=4.7946 +/- 0.1298 BAR free energy: 4.7946 +/- 0.1298 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8044 +/- 0.4437, Sum=4.0305 +/- 0.1166 Interval 2, DeltaF=1.8505 +/- 0.2550, Sum=5.1266 +/- 0.1228 Interval 3, DeltaF=3.1175 +/- 0.3371, Sum=6.9732 +/- 0.1400 Interval 4, DeltaF=3.4692 +/- 0.3974, Sum=9.0282 +/- 0.1684 Interval 5, DeltaF=1.2689 +/- 0.3553, Sum=9.7798 +/- 0.1843 Interval 6, DeltaF=-0.5616 +/- 0.2164, Sum=9.4471 +/- 0.1863 Interval 7, DeltaF=-1.5919 +/- 0.2481, Sum=8.5041 +/- 0.1899 Interval 8, DeltaF=-2.4266 +/- 0.3215, Sum=7.0668 +/- 0.1995 Interval 9, DeltaF=-2.9128 +/- 0.4159, Sum=5.3414 +/- 0.2243 Interval 10, DeltaF=-1.0742 +/- 0.2269, Sum=4.7051 +/- 0.2263 Unopt. BAR free energy: 4.7051 +/- 0.2263 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8412 +/- 0.2995, Sum=4.0523 +/- 0.0531 Interval 2, DeltaF=1.8739 +/- 0.1951, Sum=5.1623 +/- 0.0577 Interval 3, DeltaF=3.1661 +/- 0.2520, Sum=7.0377 +/- 0.0689 Interval 4, DeltaF=3.5059 +/- 0.3147, Sum=9.1143 +/- 0.0905 Interval 5, DeltaF=1.2360 +/- 0.3347, Sum=9.8465 +/- 0.1122 Interval 6, DeltaF=-0.5605 +/- 0.2448, Sum=9.5145 +/- 0.1177 Interval 7, DeltaF=-1.6354 +/- 0.2828, Sum=8.5457 +/- 0.1269 Interval 8, DeltaF=-2.3663 +/- 0.2578, Sum=7.1441 +/- 0.1328 Interval 9, DeltaF=-2.9062 +/- 0.2129, Sum=5.4227 +/- 0.1355 Interval 10, DeltaF=-1.0642 +/- 0.1501, Sum=4.7923 +/- 0.1362 Postopt. BAR free energy: 4.7923 +/- 0.1362 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.40957926] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.73003901] relative max_delta = 2.791647e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9390 relative max_delta = 4.230934e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.8166 relative max_delta = 2.754435e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8415 relative max_delta = 3.640538e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8415 relative max_delta = 7.135349e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8415 relative max_delta = 2.674336e-14 Converged to tolerance of 2.674336e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8415 Final dimensionless free energies f_k = [ 0. 6.84150229] Computing normalized weights... Interval 1, DeltaF=6.8415 +/- 0.2993, Sum=4.0525 +/- 0.0530 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 977 N_k = [500 477] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.45570442] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.76758587] relative max_delta = 1.764449e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7782 relative max_delta = 5.953080e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.8734 relative max_delta = 5.084704e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.8734 relative max_delta = 5.682809e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.8734 relative max_delta = 3.870985e-13 Converged to tolerance of 3.870985e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.8734 Final dimensionless free energies f_k = [ 0. 1.87341917] Computing normalized weights... Interval 2, DeltaF=1.8734 +/- 0.1945, Sum=5.1622 +/- 0.0576 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 894 N_k = [477 417] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.65202644] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.44715125] relative max_delta = 3.249185e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5225 relative max_delta = 2.986586e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1926 relative max_delta = 2.099006e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1674 relative max_delta = 7.965675e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1674 relative max_delta = 6.674874e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1674 relative max_delta = 4.823983e-12 Converged to tolerance of 4.823983e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1674 Final dimensionless free energies f_k = [ 0. 3.16736874] Computing normalized weights... Interval 3, DeltaF=3.1674 +/- 0.2503, Sum=7.0383 +/- 0.0685 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 754 N_k = [417 337] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.07684237] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.86553817] relative max_delta = 4.227712e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.0707 relative max_delta = 9.905790e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.8218 relative max_delta = 4.582007e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.5118 relative max_delta = 8.826700e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4987 relative max_delta = 3.741319e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4987 relative max_delta = 6.758926e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4987 relative max_delta = 2.205243e-11 Converged to tolerance of 2.205243e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4987 Final dimensionless free energies f_k = [ 0. 3.49871543] Computing normalized weights... Interval 4, DeltaF=3.4987 +/- 0.2970, Sum=9.1107 +/- 0.0861 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 837 N_k = [337 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.31877448] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.56260385] relative max_delta = 4.333944e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6341 relative max_delta = 1.127294e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2686 relative max_delta = 5.001656e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2325 relative max_delta = 2.927914e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2324 relative max_delta = 1.108776e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2324 relative max_delta = 1.578848e-09 Converged to tolerance of 1.578848e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2324 Final dimensionless free energies f_k = [ 0. 1.23236435] Computing normalized weights... Interval 5, DeltaF=1.2324 +/- 0.3292, Sum=9.8407 +/- 0.1074 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 871 N_k = [500 371] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.36363694] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.48945052] relative max_delta = 2.570507e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4967 relative max_delta = 1.451425e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5616 relative max_delta = 1.156815e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5620 relative max_delta = 7.248376e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5620 relative max_delta = 2.933964e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5620 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5620 Final dimensionless free energies f_k = [ 0. -0.56203668] Computing normalized weights... Interval 6, DeltaF=-0.5620 +/- 0.2298, Sum=9.5078 +/- 0.1119 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 614 N_k = [371 243] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98792327] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35478494] relative max_delta = 2.707896e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3809 relative max_delta = 1.894166e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6175 relative max_delta = 1.462377e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6228 relative max_delta = 3.265238e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6228 relative max_delta = 1.761330e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6228 relative max_delta = 5.132484e-13 Converged to tolerance of 5.132484e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6228 Final dimensionless free energies f_k = [ 0. -1.62278015] Computing normalized weights... Interval 7, DeltaF=-1.6228 +/- 0.2701, Sum=8.5466 +/- 0.1199 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 460 N_k = [243 217] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.63979082] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.12198249] relative max_delta = 2.272364e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1462 relative max_delta = 1.130336e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3644 relative max_delta = 9.228367e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3641 relative max_delta = 1.266749e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3641 relative max_delta = 1.624953e-10 Converged to tolerance of 1.624953e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3641 Final dimensionless free energies f_k = [ 0. -2.36414214] Computing normalized weights... Interval 8, DeltaF=-2.3641 +/- 0.2565, Sum=7.1462 +/- 0.1261 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 550 N_k = [217 333] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34815779] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.78053561] relative max_delta = 1.555016e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7933 relative max_delta = 4.570962e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9079 relative max_delta = 3.940818e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9066 relative max_delta = 4.339894e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9066 relative max_delta = 4.839277e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9066 relative max_delta = 6.111382e-16 Converged to tolerance of 6.111382e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9066 Final dimensionless free energies f_k = [ 0. -2.90663711] Computing normalized weights... Interval 9, DeltaF=-2.9066 +/- 0.2167, Sum=5.4245 +/- 0.1292 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 745 N_k = [333 412] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9827601] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.05702337] relative max_delta = 7.025698e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0577 relative max_delta = 6.029869e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0634 relative max_delta = 5.397218e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0634 relative max_delta = 1.578436e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0634 relative max_delta = 1.317569e-13 Converged to tolerance of 1.317569e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0634 Final dimensionless free energies f_k = [ 0. -1.06339885] Computing normalized weights... Interval 10, DeltaF=-1.0634 +/- 0.1469, Sum=4.7946 +/- 0.1298 Pairwise MBAR free energy: 4.7946 +/- 0.1298 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4307 N_k = [500 500 477 417 337 500 371 243 217 333 412] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.01799813 2.03998062 1.8280173 1.56445684 1.59044422 1.57311628 1.55136708 1.48071511 0.90927504 0.48104244] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.00409221 3.39288546 3.3416044 2.90748539 2.90391103 2.8506593 2.73526191 2.48090634 1.46696809 0.86183377] relative max_delta = 4.461062e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2698 3.7939 4.2541 4.4396 4.5813 4.4830 4.2595 3.8416 2.6027 1.9449 relative max_delta = 3.661352e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8091 7.5668 12.0055 17.1440 18.5475 18.0374 16.7810 14.7733 11.5167 10.4024 relative max_delta = 7.529975e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8189 8.8061 11.8980 15.9160 17.1515 16.5931 14.9636 12.6358 9.6741 8.6156 relative max_delta = 1.246275e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8362 8.7173 11.8379 15.3501 16.5804 16.0164 14.3736 12.0128 9.0821 8.0218 relative max_delta = 3.757073e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8355 8.7175 11.8305 15.3002 16.5322 15.9682 14.3254 11.9644 9.0339 7.9736 relative max_delta = 3.020620e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8355 8.7175 11.8305 15.2998 16.5319 15.9679 14.3251 11.9640 9.0335 7.9733 relative max_delta = 2.212693e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8355 8.7175 11.8305 15.2998 16.5319 15.9679 14.3251 11.9640 9.0335 7.9733 relative max_delta = 1.230957e-09 Converged to tolerance of 1.230957e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8355 8.7175 11.8305 15.2998 16.5319 15.9679 14.3251 11.9640 9.0335 7.9733 Final dimensionless free energies f_k = [ 0. 6.83553928 8.71752823 11.83047694 15.29981367 16.53187899 15.96785395 14.32506539 11.96401248 9.03353337 7.97326595] Computing normalized weights... DeltaMij: [[ 0. 4.04894519 5.16371752 7.0076333 9.06265101 9.79244931 9.45835621 8.4852712 7.08673139 5.35089917 4.72286318] [-4.04894519 0. 1.11477233 2.95868811 5.01370582 5.74350412 5.40941102 4.43632601 3.0377862 1.30195398 0.67391799] [-5.16371752 -1.11477233 0. 1.84391577 3.89893349 4.62873179 4.29463869 3.32155368 1.92301387 0.18718165 -0.44085434] [-7.0076333 -2.95868811 -1.84391577 0. 2.05501771 2.78481601 2.45072291 1.4776379 0.07909809 -1.65673413 -2.28477012] [-9.06265101 -5.01370582 -3.89893349 -2.05501771 0. 0.7297983 0.3957052 -0.57737981 -1.97591962 -3.71175184 -4.33978783] [-9.79244931 -5.74350412 -4.62873179 -2.78481601 -0.7297983 0. -0.3340931 -1.30717811 -2.70571792 -4.44155014 -5.06958613] [-9.45835621 -5.40941102 -4.29463869 -2.45072291 -0.3957052 0.3340931 0. -0.97308501 -2.37162482 -4.10745704 -4.73549303] [-8.4852712 -4.43632601 -3.32155368 -1.4776379 0.57737981 1.30717811 0.97308501 0. -1.39853981 -3.13437203 -3.76240802] [-7.08673139 -3.0377862 -1.92301387 -0.07909809 1.97591962 2.70571792 2.37162482 1.39853981 0. -1.73583222 -2.36386821] [-5.35089917 -1.30195398 -0.18718165 1.65673413 3.71175184 4.44155014 4.10745704 3.13437203 1.73583222 0. -0.62803599] [-4.72286318 -0.67391799 0.44085434 2.28477012 4.33978783 5.06958613 4.73549303 3.76240802 2.36386821 0.62803599 0. ]] dDeltaMij: [[ 0. 0.05209692 0.06411452 0.07676623 0.09597859 0.12117818 0.12870937 0.13940339 0.14961936 0.15551935 0.157571 ] [ 0.05209692 0. 0.02135672 0.04646492 0.07404062 0.10466324 0.11329759 0.1253138 0.13658768 0.14302626 0.14525448] [ 0.06411452 0.02135672 0. 0.03416369 0.06728873 0.10000402 0.10900803 0.12144939 0.13305112 0.13965285 0.14193403] [ 0.07676623 0.04646492 0.03416369 0. 0.05092936 0.0897405 0.09967668 0.11314872 0.12552004 0.13249754 0.13489978] [ 0.09597859 0.07404062 0.06728873 0.05092936 0. 0.06248679 0.07602435 0.09299208 0.1077039 0.11576032 0.11850234] [ 0.12117818 0.10466324 0.10000402 0.0897405 0.06248679 0. 0.02981795 0.06091571 0.08165157 0.09201565 0.09544217] [ 0.12870937 0.11329759 0.10900803 0.09967668 0.07602435 0.02981795 0. 0.04137048 0.06778316 0.080026 0.08394494] [ 0.13940339 0.1253138 0.12144939 0.11314872 0.09299208 0.06091571 0.04137048 0. 0.03516132 0.05323211 0.05898389] [ 0.14961936 0.13658768 0.13305112 0.12552004 0.1077039 0.08165157 0.06778316 0.03516132 0. 0.02323034 0.03224939] [ 0.15551935 0.14302626 0.13965285 0.13249754 0.11576032 0.09201565 0.080026 0.05323211 0.02323034 0. 0.01139644] [ 0.157571 0.14525448 0.14193403 0.13489978 0.11850234 0.09544217 0.08394494 0.05898389 0.03224939 0.01139644 0. ]] Replica 31 / 40 Computing statistical inefficiencies: lambda 0: g = 1.419 lambda 1: g = 1.999 lambda 2: g = 2.196 lambda 3: g = 1.438 lambda 4: g = 1.597 lambda 5: g = 2.100 lambda 6: g = 1.794 lambda 7: g = 1.397 lambda 8: g = 1.486 lambda 9: g = 1.796 lambda 10: g = 1.500 Subsampling data to produce uncorrelated samples... number of samples per lambda: [500 500 427 500 443 432 295 205 209 440 451] Method: EXP Forward EXP: Interval 1, DeltaF=6.8763 +/- 0.6024, Sum=4.0731 +/- 0.2150 Interval 2, DeltaF=1.9597 +/- 0.2427, Sum=5.2339 +/- 0.2178 Interval 3, DeltaF=3.7304 +/- 0.3144, Sum=7.4436 +/- 0.2255 Interval 4, DeltaF=3.9948 +/- 0.3813, Sum=9.8099 +/- 0.2414 Interval 5, DeltaF=0.9379 +/- 0.8688, Sum=10.3654 +/- 0.5081 Interval 6, DeltaF=-0.4590 +/- 0.3394, Sum=10.0935 +/- 0.5127 Interval 7, DeltaF=-1.9482 +/- 0.6326, Sum=8.9396 +/- 0.5648 Interval 8, DeltaF=-2.3967 +/- 0.3267, Sum=7.5199 +/- 0.5684 Interval 9, DeltaF=-2.9594 +/- 0.2873, Sum=5.7670 +/- 0.5705 Interval 10, DeltaF=-1.1180 +/- 0.1695, Sum=5.1047 +/- 0.5707 Forward EXP free energy: 5.1047 +/- 0.5707 Reverse EXP: Interval 1, DeltaF=6.8857 +/- 0.5631, Sum=4.0786 +/- 0.1878 Interval 2, DeltaF=2.0405 +/- 0.3718, Sum=5.2873 +/- 0.2049 Interval 3, DeltaF=3.6204 +/- 0.3896, Sum=7.4318 +/- 0.2237 Interval 4, DeltaF=3.3063 +/- 0.3791, Sum=9.3902 +/- 0.2394 Interval 5, DeltaF=0.9815 +/- 0.3985, Sum=9.9716 +/- 0.2572 Interval 6, DeltaF=-0.5475 +/- 0.3034, Sum=9.6472 +/- 0.2629 Interval 7, DeltaF=-1.8709 +/- 0.4039, Sum=8.5391 +/- 0.2801 Interval 8, DeltaF=-2.1935 +/- 0.3982, Sum=7.2398 +/- 0.2954 Interval 9, DeltaF=-2.9923 +/- 0.2836, Sum=5.4673 +/- 0.2993 Interval 10, DeltaF=-1.0081 +/- 0.2042, Sum=4.8702 +/- 0.3003 Reverse EXP free energy: 4.8702 +/- 0.3003 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8810 +/- 0.2623, Sum=4.0759 +/- 0.0407 Interval 2, DeltaF=2.0001 +/- 0.0818, Sum=5.2606 +/- 0.0409 Interval 3, DeltaF=3.6754 +/- 0.0986, Sum=7.4377 +/- 0.0413 Interval 4, DeltaF=3.6505 +/- 0.1112, Sum=9.6000 +/- 0.0420 Interval 5, DeltaF=0.9597 +/- 0.4198, Sum=10.1685 +/- 0.1125 Interval 6, DeltaF=-0.5033 +/- 0.0802, Sum=9.8704 +/- 0.1126 Interval 7, DeltaF=-1.9095 +/- 0.2352, Sum=8.7393 +/- 0.1173 Interval 8, DeltaF=-2.2951 +/- 0.1040, Sum=7.3798 +/- 0.1174 Interval 9, DeltaF=-2.9759 +/- 0.0627, Sum=5.6171 +/- 0.1175 Interval 10, DeltaF=-1.0631 +/- 0.0276, Sum=4.9874 +/- 0.1175 Average EXP free energy: 4.9874 +/- 0.1175 Interval 1, DeltaF=6.8857 +/- 0.2440, Sum=4.0786 +/- 0.0353 Interval 2, DeltaF=1.9597 +/- 0.3976, Sum=5.2395 +/- 0.1001 Interval 3, DeltaF=3.6204 +/- 0.3942, Sum=7.3840 +/- 0.1359 Interval 4, DeltaF=3.9948 +/- 0.4292, Sum=9.7502 +/- 0.1743 Interval 5, DeltaF=0.9815 +/- 0.4565, Sum=10.3316 +/- 0.2136 Interval 6, DeltaF=-0.4590 +/- 0.9379, Sum=10.0597 +/- 0.5632 Interval 7, DeltaF=-1.8709 +/- 0.4992, Sum=8.9515 +/- 0.5822 Interval 8, DeltaF=-2.3967 +/- 1.0412, Sum=7.5319 +/- 0.8667 Interval 9, DeltaF=-2.9923 +/- 0.5464, Sum=5.7594 +/- 0.8846 Interval 10, DeltaF=-1.1180 +/- 1.0485, Sum=5.0972 +/- 1.0984 Double-Wide EXP free energy: 5.0972 +/- 1.0984 Method: BAR Interval 1, DeltaF=6.7678 +/- 0.2932, Sum=4.0088 +/- 0.0509 Interval 2, DeltaF=1.9640 +/- 0.1939, Sum=5.1722 +/- 0.0556 Interval 3, DeltaF=3.3875 +/- 0.2497, Sum=7.1787 +/- 0.0667 Interval 4, DeltaF=3.4015 +/- 0.2897, Sum=9.1936 +/- 0.0832 Interval 5, DeltaF=1.2916 +/- 0.3146, Sum=9.9586 +/- 0.1018 Interval 6, DeltaF=-0.5576 +/- 0.2468, Sum=9.6283 +/- 0.1080 Interval 7, DeltaF=-1.7908 +/- 0.2899, Sum=8.5675 +/- 0.1189 Interval 8, DeltaF=-2.4055 +/- 0.2619, Sum=7.1427 +/- 0.1257 Interval 9, DeltaF=-2.9838 +/- 0.2179, Sum=5.3753 +/- 0.1288 Interval 10, DeltaF=-1.0798 +/- 0.1405, Sum=4.7357 +/- 0.1293 BAR free energy: 4.7357 +/- 0.1293 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8829 +/- 0.4555, Sum=4.0770 +/- 0.1229 Interval 2, DeltaF=1.9526 +/- 0.2728, Sum=5.2336 +/- 0.1306 Interval 3, DeltaF=3.4876 +/- 0.3202, Sum=7.2995 +/- 0.1440 Interval 4, DeltaF=3.4064 +/- 0.3795, Sum=9.3172 +/- 0.1674 Interval 5, DeltaF=1.3456 +/- 0.3508, Sum=10.1142 +/- 0.1826 Interval 6, DeltaF=-0.5469 +/- 0.2308, Sum=9.7903 +/- 0.1853 Interval 7, DeltaF=-1.8130 +/- 0.2734, Sum=8.7164 +/- 0.1905 Interval 8, DeltaF=-2.3057 +/- 0.3465, Sum=7.3506 +/- 0.2033 Interval 9, DeltaF=-2.9778 +/- 0.4373, Sum=5.5867 +/- 0.2328 Interval 10, DeltaF=-1.0585 +/- 0.2042, Sum=4.9597 +/- 0.2341 Unopt. BAR free energy: 4.9597 +/- 0.2341 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7561 +/- 0.2937, Sum=4.0019 +/- 0.0511 Interval 2, DeltaF=1.9643 +/- 0.1938, Sum=5.1654 +/- 0.0557 Interval 3, DeltaF=3.3795 +/- 0.2515, Sum=7.1673 +/- 0.0671 Interval 4, DeltaF=3.3991 +/- 0.3006, Sum=9.1807 +/- 0.0859 Interval 5, DeltaF=1.3053 +/- 0.3229, Sum=9.9538 +/- 0.1058 Interval 6, DeltaF=-0.5671 +/- 0.2629, Sum=9.6179 +/- 0.1134 Interval 7, DeltaF=-1.7901 +/- 0.2957, Sum=8.5576 +/- 0.1247 Interval 8, DeltaF=-2.3922 +/- 0.2650, Sum=7.1406 +/- 0.1315 Interval 9, DeltaF=-2.9838 +/- 0.2168, Sum=5.3732 +/- 0.1344 Interval 10, DeltaF=-1.0783 +/- 0.1418, Sum=4.7345 +/- 0.1349 Postopt. BAR free energy: 4.7345 +/- 0.1349 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.58864541] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.8569695] relative max_delta = 2.611349e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0473 relative max_delta = 3.770727e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7566 relative max_delta = 2.529801e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7678 relative max_delta = 1.664136e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7678 relative max_delta = 1.702007e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7678 relative max_delta = 1.837295e-15 Converged to tolerance of 1.837295e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7678 Final dimensionless free energies f_k = [ 0. 6.7678293] Computing normalized weights... Interval 1, DeltaF=6.7678 +/- 0.2932, Sum=4.0088 +/- 0.0509 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 927 N_k = [500 427] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.55488326] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.86554177] relative max_delta = 1.665246e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8754 relative max_delta = 5.261132e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9642 relative max_delta = 4.518508e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9640 relative max_delta = 9.152870e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9640 relative max_delta = 2.558402e-10 Converged to tolerance of 2.558402e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9640 Final dimensionless free energies f_k = [ 0. 1.96397946] Computing normalized weights... Interval 2, DeltaF=1.9640 +/- 0.1939, Sum=5.1722 +/- 0.0556 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 927 N_k = [427 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.71174228] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.56680359] relative max_delta = 3.331230e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6514 relative max_delta = 3.189565e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.4059 relative max_delta = 2.215469e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3876 relative max_delta = 5.430703e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3875 relative max_delta = 5.890932e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3875 relative max_delta = 6.816916e-15 Converged to tolerance of 6.816916e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3875 Final dimensionless free energies f_k = [ 0. 3.38754929] Computing normalized weights... Interval 3, DeltaF=3.3875 +/- 0.2497, Sum=7.1787 +/- 0.0667 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 943 N_k = [500 443] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.96770194] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.70710506] relative max_delta = 4.331328e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9173 relative max_delta = 1.096324e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7085 relative max_delta = 4.829979e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4116 relative max_delta = 8.701232e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4015 relative max_delta = 2.993406e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4015 relative max_delta = 3.516911e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4015 relative max_delta = 4.852735e-12 Converged to tolerance of 4.852735e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4015 Final dimensionless free energies f_k = [ 0. 3.40145329] Computing normalized weights... Interval 4, DeltaF=3.4015 +/- 0.2897, Sum=9.1936 +/- 0.0832 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 875 N_k = [443 432] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.35625767] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.62388591] relative max_delta = 4.289698e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6965 relative max_delta = 1.043151e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3381 relative max_delta = 4.794563e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2918 relative max_delta = 3.581538e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2916 relative max_delta = 2.045955e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2916 relative max_delta = 6.645226e-09 Converged to tolerance of 6.645226e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2916 Final dimensionless free energies f_k = [ 0. 1.29158075] Computing normalized weights... Interval 5, DeltaF=1.2916 +/- 0.3146, Sum=9.9586 +/- 0.1018 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 727 N_k = [432 295] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.34827136] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.47653292] relative max_delta = 2.691557e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4846 relative max_delta = 1.659443e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5571 relative max_delta = 1.301407e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5576 relative max_delta = 9.996135e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5576 relative max_delta = 6.033000e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5576 relative max_delta = 1.990970e-15 Converged to tolerance of 1.990970e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5576 Final dimensionless free energies f_k = [ 0. -0.55762935] Computing normalized weights... Interval 6, DeltaF=-0.5576 +/- 0.2468, Sum=9.6283 +/- 0.1080 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 500 N_k = [295 205] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.05187322] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.46276813] relative max_delta = 2.809023e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4948 relative max_delta = 2.142006e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7843 relative max_delta = 1.622577e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7908 relative max_delta = 3.629268e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7908 relative max_delta = 2.003932e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7908 relative max_delta = 6.110296e-13 Converged to tolerance of 6.110296e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7908 Final dimensionless free energies f_k = [ 0. -1.79080651] Computing normalized weights... Interval 7, DeltaF=-1.7908 +/- 0.2899, Sum=8.5675 +/- 0.1189 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 414 N_k = [205 209] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.71578039] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.18219717] relative max_delta = 2.137372e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2046 relative max_delta = 1.016189e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.4060 relative max_delta = 8.372179e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.4055 relative max_delta = 2.292982e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.4055 relative max_delta = 4.083100e-10 Converged to tolerance of 4.083100e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.4055 Final dimensionless free energies f_k = [ 0. -2.40548631] Computing normalized weights... Interval 8, DeltaF=-2.4055 +/- 0.2619, Sum=7.1427 +/- 0.1257 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 649 N_k = [209 440] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34030061] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.82717607] relative max_delta = 1.722126e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8432 relative max_delta = 5.640512e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9868 relative max_delta = 4.806851e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9838 relative max_delta = 1.014731e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9838 relative max_delta = 4.340604e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9838 relative max_delta = 7.873409e-14 Converged to tolerance of 7.873409e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9838 Final dimensionless free energies f_k = [ 0. -2.98375446] Computing normalized weights... Interval 9, DeltaF=-2.9838 +/- 0.2179, Sum=5.3753 +/- 0.1288 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 891 N_k = [440 451] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.99354186] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.07284852] relative max_delta = 7.392158e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0735 relative max_delta = 6.446616e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0798 relative max_delta = 5.768392e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0798 relative max_delta = 3.875764e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0798 relative max_delta = 2.878973e-15 Converged to tolerance of 2.878973e-15 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0798 Final dimensionless free energies f_k = [ 0. -1.0797687] Computing normalized weights... Interval 10, DeltaF=-1.0798 +/- 0.1405, Sum=4.7357 +/- 0.1293 Pairwise MBAR free energy: 4.7357 +/- 0.1293 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4402 N_k = [500 500 427 500 443 432 295 205 209 440 451] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.01262238 1.99279451 1.88268905 1.50341067 1.65884995 1.70007977 1.71823983 1.67014296 1.03673695 0.51581228] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.98318337 3.34539428 3.40720475 2.82162535 3.04597954 3.08212218 3.01890246 2.78289498 1.67284348 0.97218374] relative max_delta = 4.474388e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2496 3.7552 4.3325 4.3844 4.7340 4.7203 4.5355 4.1248 2.7928 2.0478 relative max_delta = 3.565805e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7753 7.5953 12.1312 17.3291 18.7624 18.2862 16.9386 14.8475 11.5405 10.4106 relative max_delta = 7.476847e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7562 8.8530 12.1989 16.1338 17.4201 16.8663 15.1205 12.7758 9.7819 8.6975 relative max_delta = 1.189282e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7666 8.7375 12.1106 15.5105 16.7946 16.2339 14.4767 12.1023 9.1395 8.0541 relative max_delta = 4.009984e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7657 8.7374 12.1018 15.4603 16.7458 16.1851 14.4279 12.0532 9.0907 8.0053 relative max_delta = 2.997609e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7657 8.7374 12.1017 15.4600 16.7455 16.1848 14.4276 12.0529 9.0904 8.0050 relative max_delta = 1.811347e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7657 8.7374 12.1017 15.4600 16.7455 16.1848 14.4276 12.0529 9.0904 8.0050 relative max_delta = 6.840278e-10 Converged to tolerance of 6.840278e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7657 8.7374 12.1017 15.4600 16.7455 16.1848 14.4276 12.0529 9.0904 8.0050 Final dimensionless free energies f_k = [ 0. 6.76568804 8.73741072 12.10171322 15.46001227 16.74547403 16.18477792 14.42758514 12.05291067 9.09035995 8.0050166 ] Computing normalized weights... DeltaMij: [[ 0. 4.00756969 5.17549467 7.16829668 9.15754262 9.91896963 9.58684838 8.54599748 7.13938911 5.38455968 4.74167028] [-4.00756969 0. 1.16792498 3.16072699 5.14997293 5.91139994 5.5792787 4.53842779 3.13181942 1.37698999 0.73410059] [-5.17549467 -1.16792498 0. 1.99280201 3.98204796 4.74347496 4.41135372 3.37050281 1.96389444 0.20906501 -0.43382439] [-7.16829668 -3.16072699 -1.99280201 0. 1.98924594 2.75067295 2.41855171 1.3777008 -0.02890757 -1.783737 -2.4266264 ] [-9.15754262 -5.14997293 -3.98204796 -1.98924594 0. 0.76142701 0.42930576 -0.61154515 -2.01815352 -3.77298294 -4.41587234] [-9.91896963 -5.91139994 -4.74347496 -2.75067295 -0.76142701 0. -0.33212124 -1.37297215 -2.77958052 -4.53440995 -5.17729935] [-9.58684838 -5.5792787 -4.41135372 -2.41855171 -0.42930576 0.33212124 0. -1.04085091 -2.44745928 -4.2022887 -4.8451781 ] [-8.54599748 -4.53842779 -3.37050281 -1.3777008 0.61154515 1.37297215 1.04085091 0. -1.40660837 -3.1614378 -3.8043272 ] [-7.13938911 -3.13181942 -1.96389444 0.02890757 2.01815352 2.77958052 2.44745928 1.40660837 0. -1.75482943 -2.39771883] [-5.38455968 -1.37698999 -0.20906501 1.783737 3.77298294 4.53440995 4.2022887 3.1614378 1.75482943 0. -0.6428894 ] [-4.74167028 -0.73410059 0.43382439 2.4266264 4.41587234 5.17729935 4.8451781 3.8043272 2.39771883 0.6428894 0. ]] dDeltaMij: [[ 0. 0.04996453 0.06209689 0.0748073 0.09324881 0.11495896 0.12473749 0.13831285 0.1494552 0.15556381 0.15736835] [ 0.04996453 0. 0.02115234 0.04578661 0.07210395 0.09858621 0.10983223 0.12503648 0.13726082 0.14388807 0.14583715] [ 0.06209689 0.02115234 0. 0.03318769 0.06503616 0.09354106 0.10532714 0.12109835 0.13368329 0.14047941 0.14247513] [ 0.0748073 0.04578661 0.03318769 0. 0.04902348 0.08315736 0.09622454 0.11327027 0.12663557 0.13379017 0.13588417] [ 0.09324881 0.07210395 0.06503616 0.04902348 0. 0.0569023 0.07466837 0.09563953 0.11114536 0.11923312 0.1215781 ] [ 0.11495896 0.09858621 0.09354106 0.08315736 0.0569023 0. 0.03496542 0.06885704 0.08917504 0.09907073 0.10188073] [ 0.12473749 0.10983223 0.10532714 0.09622454 0.07466837 0.03496542 0. 0.04543742 0.07198692 0.08399569 0.08729428] [ 0.13831285 0.12503648 0.12109835 0.11327027 0.09563953 0.06885704 0.04543742 0. 0.03602254 0.05412349 0.05913114] [ 0.1494552 0.13726082 0.13368329 0.12663557 0.11114536 0.08917504 0.07198692 0.03602254 0. 0.02287047 0.03092909] [ 0.15556381 0.14388807 0.14047941 0.13379017 0.11923312 0.09907073 0.08399569 0.05412349 0.02287047 0. 0.01055752] [ 0.15736835 0.14583715 0.14247513 0.13588417 0.1215781 0.10188073 0.08729428 0.05913114 0.03092909 0.01055752 0. ]] Replica 32 / 40 Computing statistical inefficiencies: lambda 0: g = 2.060 lambda 1: g = 1.259 lambda 2: g = 1.551 lambda 3: g = 1.778 lambda 4: g = 1.074 lambda 5: g = 2.006 lambda 6: g = 1.621 lambda 7: g = 1.504 lambda 8: g = 1.651 lambda 9: g = 1.210 lambda 10: g = 1.683 Subsampling data to produce uncorrelated samples... number of samples per lambda: [489 425 500 500 447 500 408 208 233 264 379] Method: EXP Forward EXP: Interval 1, DeltaF=6.8237 +/- 0.4025, Sum=4.0419 +/- 0.0960 Interval 2, DeltaF=2.0109 +/- 0.2574, Sum=5.2330 +/- 0.1037 Interval 3, DeltaF=3.2108 +/- 0.3907, Sum=7.1349 +/- 0.1376 Interval 4, DeltaF=4.1049 +/- 0.4214, Sum=9.5664 +/- 0.1732 Interval 5, DeltaF=1.3616 +/- 0.6333, Sum=10.3729 +/- 0.2940 Interval 6, DeltaF=-0.7058 +/- 0.5297, Sum=9.9548 +/- 0.3377 Interval 7, DeltaF=-1.7517 +/- 0.4759, Sum=8.9173 +/- 0.3634 Interval 8, DeltaF=-2.1685 +/- 0.3220, Sum=7.6328 +/- 0.3685 Interval 9, DeltaF=-2.9574 +/- 0.2678, Sum=5.8810 +/- 0.3710 Interval 10, DeltaF=-1.0806 +/- 0.1915, Sum=5.2409 +/- 0.3716 Forward EXP free energy: 5.2409 +/- 0.3716 Reverse EXP: Interval 1, DeltaF=7.6086 +/- 0.8355, Sum=4.5068 +/- 0.4135 Interval 2, DeltaF=1.8793 +/- 0.2638, Sum=5.6200 +/- 0.4155 Interval 3, DeltaF=3.4631 +/- 0.5374, Sum=7.6713 +/- 0.4494 Interval 4, DeltaF=3.4842 +/- 0.3800, Sum=9.7352 +/- 0.4574 Interval 5, DeltaF=1.3558 +/- 0.4185, Sum=10.5383 +/- 0.4691 Interval 6, DeltaF=-0.5185 +/- 0.2851, Sum=10.2311 +/- 0.4715 Interval 7, DeltaF=-1.6800 +/- 0.3790, Sum=9.2360 +/- 0.4791 Interval 8, DeltaF=-2.5483 +/- 0.3789, Sum=7.7266 +/- 0.4866 Interval 9, DeltaF=-2.7344 +/- 0.3833, Sum=6.1069 +/- 0.4943 Interval 10, DeltaF=-1.1146 +/- 0.1843, Sum=5.4466 +/- 0.4947 Reverse EXP free energy: 5.4466 +/- 0.4947 Averge of forward and reverse EXP: Interval 1, DeltaF=7.2161 +/- 0.3900, Sum=4.2744 +/- 0.0901 Interval 2, DeltaF=1.9451 +/- 0.0523, Sum=5.4265 +/- 0.0901 Interval 3, DeltaF=3.3369 +/- 0.1778, Sum=7.4031 +/- 0.0920 Interval 4, DeltaF=3.7945 +/- 0.1246, Sum=9.6508 +/- 0.0925 Interval 5, DeltaF=1.3587 +/- 0.2381, Sum=10.4556 +/- 0.0984 Interval 6, DeltaF=-0.6122 +/- 0.1590, Sum=10.0930 +/- 0.0995 Interval 7, DeltaF=-1.7158 +/- 0.1459, Sum=9.0766 +/- 0.1003 Interval 8, DeltaF=-2.3584 +/- 0.0964, Sum=7.6797 +/- 0.1005 Interval 9, DeltaF=-2.8459 +/- 0.0890, Sum=5.9939 +/- 0.1006 Interval 10, DeltaF=-1.0976 +/- 0.0272, Sum=5.3438 +/- 0.1006 Average EXP free energy: 5.3438 +/- 0.1006 Interval 1, DeltaF=7.6086 +/- 0.5372, Sum=4.5068 +/- 0.1710 Interval 2, DeltaF=2.0109 +/- 0.1836, Sum=5.6980 +/- 0.1721 Interval 3, DeltaF=3.4631 +/- 0.7952, Sum=7.7493 +/- 0.4123 Interval 4, DeltaF=4.1049 +/- 0.2874, Sum=10.1807 +/- 0.4151 Interval 5, DeltaF=1.3558 +/- 0.8513, Sum=10.9838 +/- 0.5972 Interval 6, DeltaF=-0.7058 +/- 0.5817, Sum=10.5658 +/- 0.6299 Interval 7, DeltaF=-1.6800 +/- 0.8734, Sum=9.5706 +/- 0.7753 Interval 8, DeltaF=-2.1685 +/- 0.6725, Sum=8.2861 +/- 0.8202 Interval 9, DeltaF=-2.7344 +/- 0.9013, Sum=6.6665 +/- 0.9509 Interval 10, DeltaF=-1.0806 +/- 0.6822, Sum=6.0264 +/- 0.9901 Double-Wide EXP free energy: 6.0264 +/- 0.9901 Method: BAR Interval 1, DeltaF=6.6845 +/- 0.2965, Sum=3.9595 +/- 0.0521 Interval 2, DeltaF=1.9439 +/- 0.1966, Sum=5.1109 +/- 0.0569 Interval 3, DeltaF=3.2152 +/- 0.2405, Sum=7.0154 +/- 0.0664 Interval 4, DeltaF=3.5282 +/- 0.2838, Sum=9.1053 +/- 0.0818 Interval 5, DeltaF=1.2535 +/- 0.3116, Sum=9.8478 +/- 0.1000 Interval 6, DeltaF=-0.5141 +/- 0.2278, Sum=9.5433 +/- 0.1046 Interval 7, DeltaF=-1.6287 +/- 0.2754, Sum=8.5785 +/- 0.1138 Interval 8, DeltaF=-2.3972 +/- 0.2582, Sum=7.1586 +/- 0.1205 Interval 9, DeltaF=-2.9795 +/- 0.2217, Sum=5.3937 +/- 0.1240 Interval 10, DeltaF=-1.0877 +/- 0.1536, Sum=4.7494 +/- 0.1247 BAR free energy: 4.7494 +/- 0.1247 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.7917 +/- 0.4953, Sum=4.0230 +/- 0.1453 Interval 2, DeltaF=1.9781 +/- 0.2463, Sum=5.1947 +/- 0.1497 Interval 3, DeltaF=3.1832 +/- 0.3195, Sum=7.0802 +/- 0.1614 Interval 4, DeltaF=3.5520 +/- 0.3809, Sum=9.1842 +/- 0.1829 Interval 5, DeltaF=1.1969 +/- 0.3374, Sum=9.8932 +/- 0.1949 Interval 6, DeltaF=-0.5146 +/- 0.2187, Sum=9.5884 +/- 0.1970 Interval 7, DeltaF=-1.6141 +/- 0.2323, Sum=8.6323 +/- 0.1996 Interval 8, DeltaF=-2.5165 +/- 0.3494, Sum=7.1417 +/- 0.2122 Interval 9, DeltaF=-2.8401 +/- 0.3981, Sum=5.4594 +/- 0.2321 Interval 10, DeltaF=-1.0953 +/- 0.2499, Sum=4.8106 +/- 0.2350 Unopt. BAR free energy: 4.8106 +/- 0.2350 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6892 +/- 0.2965, Sum=3.9623 +/- 0.0521 Interval 2, DeltaF=1.9430 +/- 0.1975, Sum=5.1132 +/- 0.0570 Interval 3, DeltaF=3.2145 +/- 0.2412, Sum=7.0173 +/- 0.0666 Interval 4, DeltaF=3.5235 +/- 0.2704, Sum=9.1044 +/- 0.0794 Interval 5, DeltaF=1.2429 +/- 0.3171, Sum=9.8406 +/- 0.0993 Interval 6, DeltaF=-0.5150 +/- 0.2413, Sum=9.5356 +/- 0.1051 Interval 7, DeltaF=-1.6378 +/- 0.2900, Sum=8.5654 +/- 0.1163 Interval 8, DeltaF=-2.4204 +/- 0.2641, Sum=7.1318 +/- 0.1234 Interval 9, DeltaF=-2.9798 +/- 0.2214, Sum=5.3667 +/- 0.1268 Interval 10, DeltaF=-1.0882 +/- 0.1609, Sum=4.7221 +/- 0.1277 Postopt. BAR free energy: 4.7221 +/- 0.1277 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 914 N_k = [489 425] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.70787285] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.94230487] relative max_delta = 2.497685e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.1180 relative max_delta = 3.433536e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6919 relative max_delta = 2.351930e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6845 relative max_delta = 1.109632e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6845 relative max_delta = 3.441240e-09 Converged to tolerance of 3.441240e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6845 Final dimensionless free energies f_k = [ 0. 6.68451202] Computing normalized weights... Interval 1, DeltaF=6.6845 +/- 0.2965, Sum=3.9595 +/- 0.0521 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 925 N_k = [425 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.50576563] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.83359743] relative max_delta = 1.787916e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8446 relative max_delta = 5.959025e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9436 relative max_delta = 5.093143e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9439 relative max_delta = 1.591654e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9439 relative max_delta = 1.932524e-09 Converged to tolerance of 1.932524e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9439 Final dimensionless free energies f_k = [ 0. 1.94388803] Computing normalized weights... Interval 2, DeltaF=1.9439 +/- 0.1966, Sum=5.1109 +/- 0.0569 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.76362312] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.55378555] relative max_delta = 3.094083e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6214 relative max_delta = 2.578209e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2258 relative max_delta = 1.873722e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2152 relative max_delta = 3.284335e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2152 relative max_delta = 1.708502e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2152 relative max_delta = 5.524814e-16 Converged to tolerance of 5.524814e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2152 Final dimensionless free energies f_k = [ 0. 3.21523352] Computing normalized weights... Interval 3, DeltaF=3.2152 +/- 0.2405, Sum=7.0154 +/- 0.0664 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 947 N_k = [500 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.99383902] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.75926866] relative max_delta = 4.350840e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9895 relative max_delta = 1.157250e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.9289 relative max_delta = 4.936274e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.5467 relative max_delta = 1.077838e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.5283 relative max_delta = 5.206143e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.5282 relative max_delta = 1.247636e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.5282 relative max_delta = 7.168982e-11 Converged to tolerance of 7.168982e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.5282 Final dimensionless free energies f_k = [ 0. 3.52824788] Computing normalized weights... Interval 4, DeltaF=3.5282 +/- 0.2838, Sum=9.1053 +/- 0.0818 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 947 N_k = [447 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.34626967] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.604123] relative max_delta = 4.268226e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6732 relative max_delta = 1.025998e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2865 relative max_delta = 4.767279e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2536 relative max_delta = 2.628205e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2535 relative max_delta = 8.454827e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2535 relative max_delta = 8.706347e-10 Converged to tolerance of 8.706347e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2535 Final dimensionless free energies f_k = [ 0. 1.25345337] Computing normalized weights... Interval 5, DeltaF=1.2535 +/- 0.3116, Sum=9.8478 +/- 0.1000 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 908 N_k = [500 408] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.32859021] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.44521053] relative max_delta = 2.619442e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4521 relative max_delta = 1.516377e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5138 relative max_delta = 1.201971e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5141 relative max_delta = 5.589682e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5141 relative max_delta = 1.254024e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5141 relative max_delta = 2.375440e-15 Converged to tolerance of 2.375440e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5141 Final dimensionless free energies f_k = [ 0. -0.51411329] Computing normalized weights... Interval 6, DeltaF=-0.5141 +/- 0.2278, Sum=9.5433 +/- 0.1046 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 616 N_k = [408 208] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97742249] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35000799] relative max_delta = 2.759876e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3770 relative max_delta = 1.960097e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6215 relative max_delta = 1.507703e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6287 relative max_delta = 4.441875e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6287 relative max_delta = 3.980047e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6287 relative max_delta = 3.197524e-12 Converged to tolerance of 3.197524e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6287 Final dimensionless free energies f_k = [ 0. -1.62870858] Computing normalized weights... Interval 7, DeltaF=-1.6287 +/- 0.2754, Sum=8.5785 +/- 0.1138 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 441 N_k = [208 233] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.69637084] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.1685283] relative max_delta = 2.177318e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1916 relative max_delta = 1.051937e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3987 relative max_delta = 8.633222e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3972 relative max_delta = 5.988291e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3972 relative max_delta = 1.966610e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3972 relative max_delta = 3.705021e-16 Converged to tolerance of 3.705021e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3972 Final dimensionless free energies f_k = [ 0. -2.39722881] Computing normalized weights... Interval 8, DeltaF=-2.3972 +/- 0.2582, Sum=7.1586 +/- 0.1205 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 497 N_k = [233 264] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34565527] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.83079104] relative max_delta = 1.713782e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8458 relative max_delta = 5.263583e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9803 relative max_delta = 4.515452e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9795 relative max_delta = 2.931367e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9795 relative max_delta = 9.615599e-09 Converged to tolerance of 9.615599e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9795 Final dimensionless free energies f_k = [ 0. -2.97947267] Computing normalized weights... Interval 9, DeltaF=-2.9795 +/- 0.2217, Sum=5.3937 +/- 0.1240 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 643 N_k = [264 379] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00418935] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08108241] relative max_delta = 7.112599e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0817 relative max_delta = 6.162485e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0877 relative max_delta = 5.514993e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0877 relative max_delta = 2.781566e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0877 relative max_delta = 6.983389e-13 Converged to tolerance of 6.983389e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0877 Final dimensionless free energies f_k = [ 0. -1.08774493] Computing normalized weights... Interval 10, DeltaF=-1.0877 +/- 0.1536, Sum=4.7494 +/- 0.1247 Pairwise MBAR free energy: 4.7494 +/- 0.1247 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4353 N_k = [489 425 500 500 447 500 408 208 233 264 379] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.92939462 1.92397628 1.89329567 1.52964441 1.6218189 1.60394559 1.54901285 1.46188297 0.89914392 0.48506767] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.85982875 3.21567094 3.41165093 2.86252825 2.95798027 2.90472505 2.75351007 2.47677718 1.46338506 0.86404803] relative max_delta = 4.450500e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1188 3.6076 4.2830 4.3762 4.6055 4.5094 4.2550 3.8157 2.5748 1.9185 relative max_delta = 3.577244e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5982 7.3140 11.6689 17.1109 18.5078 18.0239 16.7812 14.7614 11.4836 10.3345 relative max_delta = 7.511608e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6617 8.7256 11.8834 15.9740 17.2364 16.7227 15.0775 12.7229 9.7250 8.6376 relative max_delta = 1.182676e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6790 8.6058 11.8350 15.3849 16.6477 16.1284 14.4653 12.0812 9.1105 8.0208 relative max_delta = 3.854962e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6776 8.6060 11.8251 15.3331 16.5973 16.0780 14.4149 12.0305 9.0600 7.9703 relative max_delta = 3.126730e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6776 8.6060 11.8250 15.3327 16.5969 16.0777 14.4145 12.0301 9.0597 7.9700 relative max_delta = 2.162048e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6776 8.6060 11.8250 15.3327 16.5969 16.0777 14.4145 12.0301 9.0597 7.9700 relative max_delta = 1.129679e-09 Converged to tolerance of 1.129679e-09 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6776 8.6060 11.8250 15.3327 16.5969 16.0777 14.4145 12.0301 9.0597 7.9700 Final dimensionless free energies f_k = [ 0. 6.67762792 8.60597996 11.82503577 15.33269302 16.59693682 16.07765483 14.41451899 12.03014106 9.05965171 7.96995996] Computing normalized weights... DeltaMij: [[ 0. 3.95540839 5.09764332 7.00441029 9.08212667 9.83098549 9.52339538 8.53825791 7.12590181 5.36637004 4.72090492] [-3.95540839 0. 1.14223492 3.0490019 5.12671828 5.87557709 5.56798698 4.58284951 3.17049342 1.41096165 0.76549653] [-5.09764332 -1.14223492 0. 1.90676697 3.98448336 4.73334217 4.42575206 3.44061459 2.02825849 0.26872672 -0.3767384 ] [-7.00441029 -3.0490019 -1.90676697 0. 2.07771638 2.8265752 2.51898509 1.53384762 0.12149152 -1.63804025 -2.28350537] [-9.08212667 -5.12671828 -3.98448336 -2.07771638 0. 0.74885881 0.4412687 -0.54386876 -1.95622486 -3.71575663 -4.36122175] [-9.83098549 -5.87557709 -4.73334217 -2.8265752 -0.74885881 0. -0.30759011 -1.29272758 -2.70508368 -4.46461545 -5.11008057] [-9.52339538 -5.56798698 -4.42575206 -2.51898509 -0.4412687 0.30759011 0. -0.98513747 -2.39749357 -4.15702534 -4.80249046] [-8.53825791 -4.58284951 -3.44061459 -1.53384762 0.54386876 1.29272758 0.98513747 0. -1.4123561 -3.17188787 -3.81735299] [-7.12590181 -3.17049342 -2.02825849 -0.12149152 1.95622486 2.70508368 2.39749357 1.4123561 0. -1.75953177 -2.40499689] [-5.36637004 -1.41096165 -0.26872672 1.63804025 3.71575663 4.46461545 4.15702534 3.17188787 1.75953177 0. -0.64546512] [-4.72090492 -0.76549653 0.3767384 2.28350537 4.36122175 5.11008057 4.80249046 3.81735299 2.40499689 0.64546512 0. ]] dDeltaMij: [[ 0. 0.05080559 0.06367373 0.07534534 0.09144707 0.11261328 0.12043913 0.13216357 0.1435615 0.1502421 0.15256184] [ 0.05080559 0. 0.02177089 0.04474139 0.06849338 0.09492471 0.10408906 0.11745704 0.13014935 0.13748322 0.14001451] [ 0.06367373 0.02177089 0. 0.0316753 0.06110053 0.08973895 0.09938261 0.11330723 0.12641687 0.13395525 0.13655195] [ 0.07534534 0.04474139 0.0316753 0. 0.04602052 0.08018331 0.09084778 0.10590059 0.11982333 0.12775138 0.13047161] [ 0.09144707 0.06849338 0.06110053 0.04602052 0. 0.05530862 0.06983232 0.0885363 0.10479184 0.11377222 0.11681842] [ 0.11261328 0.09492471 0.08973895 0.08018331 0.05530862 0. 0.0297623 0.06166714 0.08336591 0.09440472 0.09805435] [ 0.12043913 0.10408906 0.09938261 0.09084778 0.06983232 0.0297623 0. 0.0430086 0.0701579 0.08302141 0.08715023] [ 0.13216357 0.11745704 0.11330723 0.10590059 0.0885363 0.06166714 0.0430086 0. 0.03598672 0.05515943 0.0612384 ] [ 0.1435615 0.13014935 0.12641687 0.11982333 0.10479184 0.08336591 0.0701579 0.03598672 0. 0.02455904 0.03397404] [ 0.1502421 0.13748322 0.13395525 0.12775138 0.11377222 0.09440472 0.08302141 0.05515943 0.02455904 0. 0.01194611] [ 0.15256184 0.14001451 0.13655195 0.13047161 0.11681842 0.09805435 0.08715023 0.0612384 0.03397404 0.01194611 0. ]] Replica 33 / 40 Computing statistical inefficiencies: lambda 0: g = 1.568 lambda 1: g = 1.813 lambda 2: g = 1.550 lambda 3: g = 1.363 lambda 4: g = 1.199 lambda 5: g = 1.809 lambda 6: g = 2.922 lambda 7: g = 2.341 lambda 8: g = 1.000 lambda 9: g = 1.653 lambda 10: g = 1.687 Subsampling data to produce uncorrelated samples... number of samples per lambda: [297 500 370 443 500 500 464 188 231 459 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.8673 +/- 0.4737, Sum=4.0678 +/- 0.1329 Interval 2, DeltaF=1.9742 +/- 0.2508, Sum=5.2372 +/- 0.1380 Interval 3, DeltaF=3.5423 +/- 0.3341, Sum=7.3354 +/- 0.1531 Interval 4, DeltaF=3.9118 +/- 0.5100, Sum=9.6525 +/- 0.2172 Interval 5, DeltaF=0.7540 +/- 0.6242, Sum=10.0992 +/- 0.3169 Interval 6, DeltaF=-0.4351 +/- 0.3514, Sum=9.8415 +/- 0.3252 Interval 7, DeltaF=-1.7116 +/- 0.4022, Sum=8.8276 +/- 0.3391 Interval 8, DeltaF=-2.2292 +/- 0.3769, Sum=7.5072 +/- 0.3493 Interval 9, DeltaF=-2.8890 +/- 0.2963, Sum=5.7959 +/- 0.3532 Interval 10, DeltaF=-1.0412 +/- 0.1653, Sum=5.1791 +/- 0.3536 Forward EXP free energy: 5.1791 +/- 0.3536 Reverse EXP: Interval 1, DeltaF=6.8584 +/- 0.4489, Sum=4.0625 +/- 0.1194 Interval 2, DeltaF=1.8807 +/- 0.2744, Sum=5.1765 +/- 0.1274 Interval 3, DeltaF=3.3966 +/- 0.3946, Sum=7.1885 +/- 0.1573 Interval 4, DeltaF=3.0798 +/- 0.3728, Sum=9.0128 +/- 0.1776 Interval 5, DeltaF=1.3135 +/- 0.3866, Sum=9.7908 +/- 0.1984 Interval 6, DeltaF=-0.6012 +/- 0.2773, Sum=9.4347 +/- 0.2036 Interval 7, DeltaF=-1.5596 +/- 0.4331, Sum=8.5109 +/- 0.2319 Interval 8, DeltaF=-2.4964 +/- 0.3204, Sum=7.0321 +/- 0.2397 Interval 9, DeltaF=-2.8380 +/- 0.3298, Sum=5.3511 +/- 0.2483 Interval 10, DeltaF=-1.0633 +/- 0.1789, Sum=4.7213 +/- 0.2490 Reverse EXP free energy: 4.7213 +/- 0.2490 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8629 +/- 0.1641, Sum=4.0651 +/- 0.0160 Interval 2, DeltaF=1.9274 +/- 0.0534, Sum=5.2068 +/- 0.0160 Interval 3, DeltaF=3.4695 +/- 0.1043, Sum=7.2619 +/- 0.0173 Interval 4, DeltaF=3.4958 +/- 0.1605, Sum=9.3327 +/- 0.0231 Interval 5, DeltaF=1.0338 +/- 0.2271, Sum=9.9450 +/- 0.0383 Interval 6, DeltaF=-0.5182 +/- 0.0792, Sum=9.6381 +/- 0.0385 Interval 7, DeltaF=-1.6356 +/- 0.1348, Sum=8.6692 +/- 0.0399 Interval 8, DeltaF=-2.3628 +/- 0.0954, Sum=7.2696 +/- 0.0403 Interval 9, DeltaF=-2.8635 +/- 0.0761, Sum=5.5735 +/- 0.0404 Interval 10, DeltaF=-1.0522 +/- 0.0229, Sum=4.9502 +/- 0.0404 Average EXP free energy: 4.9502 +/- 0.0404 Interval 1, DeltaF=6.8584 +/- 0.1551, Sum=4.0625 +/- 0.0143 Interval 2, DeltaF=1.9742 +/- 0.2490, Sum=5.2319 +/- 0.0394 Interval 3, DeltaF=3.3966 +/- 0.2630, Sum=7.2438 +/- 0.0568 Interval 4, DeltaF=3.9118 +/- 0.3452, Sum=9.5610 +/- 0.0906 Interval 5, DeltaF=1.3135 +/- 0.3459, Sum=10.3390 +/- 0.1151 Interval 6, DeltaF=-0.4351 +/- 0.5900, Sum=10.0813 +/- 0.2362 Interval 7, DeltaF=-1.5596 +/- 0.4009, Sum=9.1575 +/- 0.2546 Interval 8, DeltaF=-2.2292 +/- 0.6326, Sum=7.8370 +/- 0.3479 Interval 9, DeltaF=-2.8380 +/- 0.4484, Sum=6.1559 +/- 0.3677 Interval 10, DeltaF=-1.0412 +/- 0.6493, Sum=5.5392 +/- 0.4445 Double-Wide EXP free energy: 5.5392 +/- 0.4445 Method: BAR Interval 1, DeltaF=6.8603 +/- 0.3119, Sum=4.0636 +/- 0.0576 Interval 2, DeltaF=1.9748 +/- 0.2004, Sum=5.2333 +/- 0.0623 Interval 3, DeltaF=3.3429 +/- 0.2553, Sum=7.2135 +/- 0.0733 Interval 4, DeltaF=3.3104 +/- 0.2867, Sum=9.1743 +/- 0.0880 Interval 5, DeltaF=1.2748 +/- 0.2992, Sum=9.9294 +/- 0.1028 Interval 6, DeltaF=-0.5037 +/- 0.2214, Sum=9.6311 +/- 0.1068 Interval 7, DeltaF=-1.5902 +/- 0.2755, Sum=8.6891 +/- 0.1159 Interval 8, DeltaF=-2.3003 +/- 0.2597, Sum=7.3266 +/- 0.1226 Interval 9, DeltaF=-2.8931 +/- 0.2091, Sum=5.6129 +/- 0.1253 Interval 10, DeltaF=-1.0538 +/- 0.1385, Sum=4.9887 +/- 0.1258 BAR free energy: 4.9887 +/- 0.1258 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8143 +/- 0.4163, Sum=4.0364 +/- 0.1027 Interval 2, DeltaF=1.9702 +/- 0.2886, Sum=5.2034 +/- 0.1139 Interval 3, DeltaF=3.3590 +/- 0.3265, Sum=7.1930 +/- 0.1302 Interval 4, DeltaF=3.3719 +/- 0.3714, Sum=9.1903 +/- 0.1537 Interval 5, DeltaF=1.1883 +/- 0.3328, Sum=9.8942 +/- 0.1671 Interval 6, DeltaF=-0.5140 +/- 0.2158, Sum=9.5897 +/- 0.1694 Interval 7, DeltaF=-1.5618 +/- 0.2093, Sum=8.6646 +/- 0.1714 Interval 8, DeltaF=-2.4140 +/- 0.3566, Sum=7.2347 +/- 0.1872 Interval 9, DeltaF=-2.8726 +/- 0.4212, Sum=5.5331 +/- 0.2147 Interval 10, DeltaF=-1.0575 +/- 0.2031, Sum=4.9067 +/- 0.2161 Unopt. BAR free energy: 4.9067 +/- 0.2161 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8631 +/- 0.3134, Sum=4.0653 +/- 0.0582 Interval 2, DeltaF=1.9748 +/- 0.2001, Sum=5.2350 +/- 0.0628 Interval 3, DeltaF=3.3394 +/- 0.2559, Sum=7.2131 +/- 0.0739 Interval 4, DeltaF=3.3215 +/- 0.2950, Sum=9.1805 +/- 0.0901 Interval 5, DeltaF=1.2617 +/- 0.3064, Sum=9.9279 +/- 0.1059 Interval 6, DeltaF=-0.4986 +/- 0.2329, Sum=9.6325 +/- 0.1106 Interval 7, DeltaF=-1.6093 +/- 0.2952, Sum=8.6793 +/- 0.1221 Interval 8, DeltaF=-2.3143 +/- 0.2652, Sum=7.3084 +/- 0.1290 Interval 9, DeltaF=-2.8931 +/- 0.2031, Sum=5.5947 +/- 0.1313 Interval 10, DeltaF=-1.0539 +/- 0.1398, Sum=4.9705 +/- 0.1318 Postopt. BAR free energy: 4.9705 +/- 0.1318 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 797 N_k = [297 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.48702309] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.83639582] relative max_delta = 2.790038e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0240 relative max_delta = 3.735083e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7339 relative max_delta = 2.539117e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8596 relative max_delta = 1.832707e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8603 relative max_delta = 1.029962e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8603 relative max_delta = 3.281369e-09 Converged to tolerance of 3.281369e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8603 Final dimensionless free energies f_k = [ 0. 6.86027487] Computing normalized weights... Interval 1, DeltaF=6.8603 +/- 0.3119, Sum=4.0636 +/- 0.0576 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 870 N_k = [500 370] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.55812403] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.87112932] relative max_delta = 1.672815e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8815 relative max_delta = 5.533460e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9751 relative max_delta = 4.739064e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9748 relative max_delta = 1.940726e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9748 relative max_delta = 2.714323e-09 Converged to tolerance of 2.714323e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9748 Final dimensionless free energies f_k = [ 0. 1.97476083] Computing normalized weights... Interval 2, DeltaF=1.9748 +/- 0.2004, Sum=5.2333 +/- 0.0623 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 813 N_k = [370 443] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.76051736] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.59441199] relative max_delta = 3.214195e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6707 relative max_delta = 2.857410e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3534 relative max_delta = 2.035762e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3429 relative max_delta = 3.136779e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3429 relative max_delta = 1.278387e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3429 relative max_delta = 5.313801e-16 Converged to tolerance of 5.313801e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3429 Final dimensionless free energies f_k = [ 0. 3.34291177] Computing normalized weights... Interval 3, DeltaF=3.3429 +/- 0.2553, Sum=7.2135 +/- 0.0733 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 943 N_k = [443 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.92251004] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.6381863] relative max_delta = 4.368711e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8451 relative max_delta = 1.121262e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6117 relative max_delta = 4.891417e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3194 relative max_delta = 8.804456e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3104 relative max_delta = 2.737937e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3104 relative max_delta = 2.744726e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3104 relative max_delta = 2.764047e-12 Converged to tolerance of 2.764047e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3104 Final dimensionless free energies f_k = [ 0. 3.31036819] Computing normalized weights... Interval 4, DeltaF=3.3104 +/- 0.2867, Sum=9.1743 +/- 0.0880 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.37049944] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.64327143] relative max_delta = 4.240387e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7114 relative max_delta = 9.579958e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3143 relative max_delta = 4.587056e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2750 relative max_delta = 3.086111e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2748 relative max_delta = 1.403418e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2748 relative max_delta = 2.894645e-09 Converged to tolerance of 2.894645e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2748 Final dimensionless free energies f_k = [ 0. 1.2747791] Computing normalized weights... Interval 5, DeltaF=1.2748 +/- 0.2992, Sum=9.9294 +/- 0.1028 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 964 N_k = [500 464] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.32720718] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.43995424] relative max_delta = 2.562700e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4463 relative max_delta = 1.422841e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5035 relative max_delta = 1.135924e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5037 relative max_delta = 3.674837e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5037 relative max_delta = 4.057381e-09 Converged to tolerance of 4.057381e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5037 Final dimensionless free energies f_k = [ 0. -0.50368306] Computing normalized weights... Interval 6, DeltaF=-0.5037 +/- 0.2214, Sum=9.6311 +/- 0.1068 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 652 N_k = [464 188] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96131004] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.32484011] relative max_delta = 2.743954e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3504 relative max_delta = 1.890972e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5820 relative max_delta = 1.463923e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5902 relative max_delta = 5.158892e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5902 relative max_delta = 6.445257e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5902 relative max_delta = 1.005569e-11 Converged to tolerance of 1.005569e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5902 Final dimensionless free energies f_k = [ 0. -1.59017618] Computing normalized weights... Interval 7, DeltaF=-1.5902 +/- 0.2755, Sum=8.6891 +/- 0.1159 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 419 N_k = [188 231] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.65708435] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.0965102] relative max_delta = 2.095987e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1171 relative max_delta = 9.714650e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3018 relative max_delta = 8.024277e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3003 relative max_delta = 6.440217e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3003 relative max_delta = 3.228778e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3003 relative max_delta = 1.158344e-15 Converged to tolerance of 1.158344e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3003 Final dimensionless free energies f_k = [ 0. -2.30029638] Computing normalized weights... Interval 8, DeltaF=-2.3003 +/- 0.2597, Sum=7.3266 +/- 0.1226 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 690 N_k = [231 459] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.36983296] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.77604419] relative max_delta = 1.463274e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7879 relative max_delta = 4.263521e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8945 relative max_delta = 3.683264e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8931 relative max_delta = 5.060304e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8931 relative max_delta = 9.135569e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8931 relative max_delta = 2.149007e-15 Converged to tolerance of 2.149007e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8931 Final dimensionless free energies f_k = [ 0. -2.89308004] Computing normalized weights... Interval 9, DeltaF=-2.8931 +/- 0.2091, Sum=5.6129 +/- 0.1253 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 959 N_k = [459 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97002965] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.04695592] relative max_delta = 7.347613e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0476 relative max_delta = 6.492232e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0538 relative max_delta = 5.808870e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0538 relative max_delta = 8.262371e-07 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0538 relative max_delta = 1.643594e-14 Converged to tolerance of 1.643594e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0538 Final dimensionless free energies f_k = [ 0. -1.05375634] Computing normalized weights... Interval 10, DeltaF=-1.0538 +/- 0.1385, Sum=4.9887 +/- 0.1258 Pairwise MBAR free energy: 4.9887 +/- 0.1258 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4452 N_k = [297 500 370 443 500 500 464 188 231 459 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.11954878 2.20529864 2.072742 1.7314474 1.91943445 1.88085752 1.86129014 1.85048289 1.30395319 0.82295148] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.18095966 3.66706037 3.70949817 3.18459871 3.44257884 3.38383541 3.28539244 3.11343309 2.13050084 1.47958827] relative max_delta = 4.412339e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.4265 4.0460 4.6000 4.6758 5.0492 4.9489 4.7526 4.4263 3.2194 2.5220 relative max_delta = 3.181953e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7716 7.6157 12.1605 17.2278 18.6080 18.1289 16.9942 15.1392 11.9160 10.8155 relative max_delta = 7.286541e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8136 8.9356 12.1987 16.0293 17.2872 16.7792 15.1893 12.9062 9.9848 8.9344 relative max_delta = 1.291747e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8471 8.8283 12.1437 15.5017 16.7606 16.2462 14.6266 12.2982 9.4173 8.3651 relative max_delta = 3.627348e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8461 8.8280 12.1358 15.4652 16.7250 16.2106 14.5909 12.2620 9.3816 8.3294 relative max_delta = 2.182653e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.8461 8.8280 12.1358 15.4650 16.7249 16.2105 14.5907 12.2618 9.3815 8.3292 relative max_delta = 9.056570e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.8461 8.8280 12.1358 15.4650 16.7249 16.2105 14.5907 12.2618 9.3815 8.3292 relative max_delta = 1.671315e-10 Converged to tolerance of 1.671315e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8461 8.8280 12.1358 15.4650 16.7249 16.2105 14.5907 12.2618 9.3815 8.3292 Final dimensionless free energies f_k = [ 0. 6.8460745 8.82803125 12.13578654 15.46504134 16.72489838 16.21047231 14.59070454 12.26181412 9.38145082 8.32922809] Computing normalized weights... DeltaMij: [[ 0. 4.05518559 5.22917259 7.18847958 9.16052152 9.9067819 9.60206813 8.64261919 7.26313042 5.55698367 4.93371285] [-4.05518559 0. 1.173987 3.13329399 5.10533593 5.85159631 5.54688254 4.5874336 3.20794483 1.50179808 0.87852726] [-5.22917259 -1.173987 0. 1.95930699 3.93134894 4.67760931 4.37289554 3.4134466 2.03395783 0.32781108 -0.29545974] [-7.18847958 -3.13329399 -1.95930699 0. 1.97204195 2.71830232 2.41358855 1.45413961 0.07465085 -1.6314959 -2.25476673] [-9.16052152 -5.10533593 -3.93134894 -1.97204195 0. 0.74626038 0.4415466 -0.51790233 -1.8973911 -3.60353785 -4.22680867] [-9.9067819 -5.85159631 -4.67760931 -2.71830232 -0.74626038 0. -0.30471377 -1.26416271 -2.64365148 -4.34979823 -4.97306905] [-9.60206813 -5.54688254 -4.37289554 -2.41358855 -0.4415466 0.30471377 0. -0.95944894 -2.33893771 -4.04508446 -4.66835528] [-8.64261919 -4.5874336 -3.4134466 -1.45413961 0.51790233 1.26416271 0.95944894 0. -1.37948877 -3.08563552 -3.70890634] [-7.26313042 -3.20794483 -2.03395783 -0.07465085 1.8973911 2.64365148 2.33893771 1.37948877 0. -1.70614675 -2.32941757] [-5.55698367 -1.50179808 -0.32781108 1.6314959 3.60353785 4.34979823 4.04508446 3.08563552 1.70614675 0. -0.62327082] [-4.93371285 -0.87852726 0.29545974 2.25476673 4.22680867 4.97306905 4.66835528 3.70890634 2.32941757 0.62327082 0. ]] dDeltaMij: [[ 0. 0.05704537 0.06890527 0.08110917 0.09753174 0.1154354 0.1226651 0.13366404 0.14491666 0.15078089 0.15260243] [ 0.05704537 0. 0.02217095 0.04730568 0.07192778 0.09479717 0.10347898 0.1163067 0.12908141 0.13563204 0.13765418] [ 0.06890527 0.02217095 0. 0.03422274 0.06439578 0.08921765 0.09839299 0.11180577 0.12504117 0.13179276 0.13387291] [ 0.08110917 0.04730568 0.03422274 0. 0.04743106 0.07780901 0.08818039 0.1029326 0.11717459 0.12435402 0.1265565 ] [ 0.09753174 0.07192778 0.06439578 0.04743106 0. 0.05164766 0.06620344 0.08486851 0.10167293 0.10987004 0.1123568 ] [ 0.1154354 0.09479717 0.08921765 0.07780901 0.05164766 0. 0.02834911 0.05984358 0.0819807 0.09194841 0.09490578] [ 0.1226651 0.10347898 0.09839299 0.08818039 0.06620344 0.02834911 0. 0.04253978 0.06982594 0.08133962 0.08466992] [ 0.13366404 0.1163067 0.11180577 0.1029326 0.08486851 0.05984358 0.04253978 0. 0.0349245 0.05206062 0.05714482] [ 0.14491666 0.12908141 0.12504117 0.11717459 0.10167293 0.0819807 0.06982594 0.0349245 0. 0.02224543 0.03038302] [ 0.15078089 0.13563204 0.13179276 0.12435402 0.10987004 0.09194841 0.08133962 0.05206062 0.02224543 0. 0.0104901 ] [ 0.15260243 0.13765418 0.13387291 0.1265565 0.1123568 0.09490578 0.08466992 0.05714482 0.03038302 0.0104901 0. ]] Replica 34 / 40 Computing statistical inefficiencies: lambda 0: g = 2.884 lambda 1: g = 1.466 lambda 2: g = 1.963 lambda 3: g = 1.564 lambda 4: g = 1.601 lambda 5: g = 1.581 lambda 6: g = 1.903 lambda 7: g = 1.446 lambda 8: g = 1.637 lambda 9: g = 1.000 lambda 10: g = 1.300 Subsampling data to produce uncorrelated samples... number of samples per lambda: [368 500 487 493 398 335 430 154 166 500 329] Method: EXP Forward EXP: Interval 1, DeltaF=6.7832 +/- 0.5561, Sum=4.0179 +/- 0.1832 Interval 2, DeltaF=1.9040 +/- 0.2557, Sum=5.1458 +/- 0.1872 Interval 3, DeltaF=3.2532 +/- 0.3494, Sum=7.0728 +/- 0.2007 Interval 4, DeltaF=3.4741 +/- 0.5376, Sum=9.1306 +/- 0.2638 Interval 5, DeltaF=1.7320 +/- 0.4882, Sum=10.1565 +/- 0.2992 Interval 6, DeltaF=-0.3657 +/- 0.3700, Sum=9.9399 +/- 0.3100 Interval 7, DeltaF=-1.3397 +/- 0.3200, Sum=9.1464 +/- 0.3159 Interval 8, DeltaF=-2.6029 +/- 0.4915, Sum=7.6046 +/- 0.3468 Interval 9, DeltaF=-2.9854 +/- 0.3268, Sum=5.8363 +/- 0.3525 Interval 10, DeltaF=-1.0861 +/- 0.1644, Sum=5.1929 +/- 0.3529 Forward EXP free energy: 5.1929 +/- 0.3529 Reverse EXP: Interval 1, DeltaF=6.9889 +/- 0.6166, Sum=4.1398 +/- 0.2252 Interval 2, DeltaF=1.9679 +/- 0.2762, Sum=5.3055 +/- 0.2297 Interval 3, DeltaF=3.0960 +/- 0.3591, Sum=7.1393 +/- 0.2421 Interval 4, DeltaF=3.3757 +/- 0.3732, Sum=9.1389 +/- 0.2557 Interval 5, DeltaF=1.2785 +/- 0.5139, Sum=9.8962 +/- 0.2998 Interval 6, DeltaF=-0.4572 +/- 0.2738, Sum=9.6254 +/- 0.3031 Interval 7, DeltaF=-1.7472 +/- 0.4800, Sum=8.5905 +/- 0.3324 Interval 8, DeltaF=-2.4324 +/- 0.3656, Sum=7.1497 +/- 0.3417 Interval 9, DeltaF=-2.8870 +/- 0.2706, Sum=5.4396 +/- 0.3444 Interval 10, DeltaF=-1.1121 +/- 0.2188, Sum=4.7809 +/- 0.3456 Reverse EXP free energy: 4.7809 +/- 0.3456 Averge of forward and reverse EXP: Interval 1, DeltaF=6.8861 +/- 0.2667, Sum=4.0789 +/- 0.0421 Interval 2, DeltaF=1.9360 +/- 0.0547, Sum=5.2256 +/- 0.0422 Interval 3, DeltaF=3.1746 +/- 0.0966, Sum=7.1060 +/- 0.0425 Interval 4, DeltaF=3.4249 +/- 0.1746, Sum=9.1347 +/- 0.0462 Interval 5, DeltaF=1.5053 +/- 0.1936, Sum=10.0264 +/- 0.0513 Interval 6, DeltaF=-0.4114 +/- 0.0849, Sum=9.7827 +/- 0.0514 Interval 7, DeltaF=-1.5434 +/- 0.1372, Sum=8.8684 +/- 0.0526 Interval 8, DeltaF=-2.5176 +/- 0.1503, Sum=7.3772 +/- 0.0543 Interval 9, DeltaF=-2.9362 +/- 0.0705, Sum=5.6380 +/- 0.0544 Interval 10, DeltaF=-1.0991 +/- 0.0299, Sum=4.9869 +/- 0.0544 Average EXP free energy: 4.9869 +/- 0.0544 Interval 1, DeltaF=6.9889 +/- 0.2926, Sum=4.1398 +/- 0.0507 Interval 2, DeltaF=1.9040 +/- 0.3403, Sum=5.2676 +/- 0.0853 Interval 3, DeltaF=3.0960 +/- 0.4336, Sum=7.1015 +/- 0.1403 Interval 4, DeltaF=3.4741 +/- 0.4307, Sum=9.1593 +/- 0.1782 Interval 5, DeltaF=1.2785 +/- 0.5120, Sum=9.9167 +/- 0.2363 Interval 6, DeltaF=-0.3657 +/- 0.5598, Sum=9.7001 +/- 0.3005 Interval 7, DeltaF=-1.7472 +/- 0.5844, Sum=8.6651 +/- 0.3623 Interval 8, DeltaF=-2.6029 +/- 0.6095, Sum=7.1233 +/- 0.4239 Interval 9, DeltaF=-2.8870 +/- 0.6303, Sum=5.4133 +/- 0.4848 Interval 10, DeltaF=-1.0861 +/- 0.6481, Sum=4.7700 +/- 0.5449 Double-Wide EXP free energy: 4.7700 +/- 0.5449 Method: BAR Interval 1, DeltaF=6.6920 +/- 0.3062, Sum=3.9639 +/- 0.0555 Interval 2, DeltaF=1.9591 +/- 0.1932, Sum=5.1244 +/- 0.0598 Interval 3, DeltaF=3.1786 +/- 0.2489, Sum=7.0072 +/- 0.0701 Interval 4, DeltaF=3.1960 +/- 0.2969, Sum=8.9003 +/- 0.0874 Interval 5, DeltaF=1.0989 +/- 0.3374, Sum=9.5512 +/- 0.1104 Interval 6, DeltaF=-0.4606 +/- 0.2296, Sum=9.2784 +/- 0.1147 Interval 7, DeltaF=-1.6265 +/- 0.2872, Sum=8.3149 +/- 0.1247 Interval 8, DeltaF=-2.3819 +/- 0.2782, Sum=6.9041 +/- 0.1329 Interval 9, DeltaF=-2.9213 +/- 0.2190, Sum=5.1737 +/- 0.1359 Interval 10, DeltaF=-1.1045 +/- 0.1451, Sum=4.5194 +/- 0.1364 BAR free energy: 4.5194 +/- 0.1364 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.7590 +/- 0.4281, Sum=4.0036 +/- 0.1086 Interval 2, DeltaF=1.9251 +/- 0.2585, Sum=5.1439 +/- 0.1155 Interval 3, DeltaF=3.1176 +/- 0.3190, Sum=6.9906 +/- 0.1303 Interval 4, DeltaF=3.0857 +/- 0.3856, Sum=8.8184 +/- 0.1573 Interval 5, DeltaF=1.0705 +/- 0.3695, Sum=9.4525 +/- 0.1769 Interval 6, DeltaF=-0.4597 +/- 0.2306, Sum=9.1802 +/- 0.1796 Interval 7, DeltaF=-1.6654 +/- 0.2104, Sum=8.1938 +/- 0.1815 Interval 8, DeltaF=-2.4071 +/- 0.3732, Sum=6.7679 +/- 0.1994 Interval 9, DeltaF=-2.8858 +/- 0.4785, Sum=5.0586 +/- 0.2412 Interval 10, DeltaF=-1.1127 +/- 0.1645, Sum=4.3995 +/- 0.2417 Unopt. BAR free energy: 4.3995 +/- 0.2417 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6930 +/- 0.3103, Sum=3.9645 +/- 0.0570 Interval 2, DeltaF=1.9596 +/- 0.1933, Sum=5.1253 +/- 0.0612 Interval 3, DeltaF=3.1772 +/- 0.2499, Sum=7.0072 +/- 0.0715 Interval 4, DeltaF=3.1862 +/- 0.3031, Sum=8.8945 +/- 0.0899 Interval 5, DeltaF=1.0967 +/- 0.3405, Sum=9.5442 +/- 0.1131 Interval 6, DeltaF=-0.4597 +/- 0.2306, Sum=9.2719 +/- 0.1174 Interval 7, DeltaF=-1.6216 +/- 0.3070, Sum=8.3113 +/- 0.1300 Interval 8, DeltaF=-2.3845 +/- 0.2827, Sum=6.8989 +/- 0.1384 Interval 9, DeltaF=-2.9227 +/- 0.2118, Sum=5.1677 +/- 0.1409 Interval 10, DeltaF=-1.1054 +/- 0.1377, Sum=4.5129 +/- 0.1413 Postopt. BAR free energy: 4.5129 +/- 0.1413 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 868 N_k = [368 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.44026869] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.77538285] relative max_delta = 2.795826e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9550 relative max_delta = 3.625429e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5819 relative max_delta = 2.471720e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6913 relative max_delta = 1.635828e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6920 relative max_delta = 1.049993e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6920 relative max_delta = 4.295434e-09 Converged to tolerance of 4.295434e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6920 Final dimensionless free energies f_k = [ 0. 6.6920415] Computing normalized weights... Interval 1, DeltaF=6.6920 +/- 0.3062, Sum=3.9639 +/- 0.0555 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 987 N_k = [500 487] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.51694659] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.84770124] relative max_delta = 1.790087e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8589 relative max_delta = 5.998003e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9592 relative max_delta = 5.120691e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9591 relative max_delta = 2.224665e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9591 relative max_delta = 3.550891e-12 Converged to tolerance of 3.550891e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9591 Final dimensionless free energies f_k = [ 0. 1.95913029] Computing normalized weights... Interval 2, DeltaF=1.9591 +/- 0.1932, Sum=5.1244 +/- 0.0598 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 980 N_k = [487 493] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.5993856] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.39773501] relative max_delta = 3.329598e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4785 relative max_delta = 3.260530e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.1991 relative max_delta = 2.252369e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1786 relative max_delta = 6.446066e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1786 relative max_delta = 2.214034e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1786 relative max_delta = 2.711806e-13 Converged to tolerance of 2.711806e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1786 Final dimensionless free energies f_k = [ 0. 3.17860879] Computing normalized weights... Interval 3, DeltaF=3.1786 +/- 0.2489, Sum=7.0072 +/- 0.0701 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 891 N_k = [493 398] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.89047988] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.57180315] relative max_delta = 4.334660e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7744 relative max_delta = 1.141984e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5048 relative max_delta = 4.937108e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2080 relative max_delta = 9.252826e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1960 relative max_delta = 3.748275e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1960 relative max_delta = 6.065386e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.1960 relative max_delta = 1.586869e-11 Converged to tolerance of 1.586869e-11 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1960 Final dimensionless free energies f_k = [ 0. 3.19597159] Computing normalized weights... Interval 4, DeltaF=3.1960 +/- 0.2969, Sum=8.9003 +/- 0.0874 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 733 N_k = [398 335] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.29140802] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.51159705] relative max_delta = 4.303954e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5749 relative max_delta = 1.101324e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.1354 relative max_delta = 4.936682e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0991 relative max_delta = 3.309441e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0989 relative max_delta = 1.591370e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0989 relative max_delta = 3.653165e-09 Converged to tolerance of 3.653165e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0989 Final dimensionless free energies f_k = [ 0. 1.09890047] Computing normalized weights... Interval 5, DeltaF=1.0989 +/- 0.3374, Sum=9.5512 +/- 0.1104 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 765 N_k = [335 430] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.310936] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.41006165] relative max_delta = 2.417335e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4151 relative max_delta = 1.216228e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4606 relative max_delta = 9.867354e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4606 relative max_delta = 6.723490e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4606 relative max_delta = 3.755675e-11 Converged to tolerance of 3.755675e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4606 Final dimensionless free energies f_k = [ 0. -0.46058589] Computing normalized weights... Interval 6, DeltaF=-0.4606 +/- 0.2296, Sum=9.2784 +/- 0.1147 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 584 N_k = [430 154] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96955069] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.34756234] relative max_delta = 2.805151e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3743 relative max_delta = 1.946450e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6171 relative max_delta = 1.501294e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6265 relative max_delta = 5.806368e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6265 relative max_delta = 8.776579e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6265 relative max_delta = 2.004615e-11 Converged to tolerance of 2.004615e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6265 Final dimensionless free energies f_k = [ 0. -1.62654301] Computing normalized weights... Interval 7, DeltaF=-1.6265 +/- 0.2872, Sum=8.3149 +/- 0.1247 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 320 N_k = [154 166] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.71065662] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.16692474] relative max_delta = 2.105602e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1885 relative max_delta = 9.873295e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3827 relative max_delta = 8.150795e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3819 relative max_delta = 3.632280e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3819 relative max_delta = 3.879425e-09 Converged to tolerance of 3.879425e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3819 Final dimensionless free energies f_k = [ 0. -2.38188029] Computing normalized weights... Interval 8, DeltaF=-2.3819 +/- 0.2782, Sum=6.9041 +/- 0.1329 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 666 N_k = [166 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.44139069] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.81724983] relative max_delta = 1.334135e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8279 relative max_delta = 3.753584e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9230 relative max_delta = 3.254264e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9213 relative max_delta = 5.695180e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9213 relative max_delta = 1.725968e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9213 relative max_delta = 1.428955e-14 Converged to tolerance of 1.428955e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9213 Final dimensionless free energies f_k = [ 0. -2.9213219] Computing normalized weights... Interval 9, DeltaF=-2.9213 +/- 0.2190, Sum=5.1737 +/- 0.1359 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 829 N_k = [500 329] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00783184] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.09664402] relative max_delta = 8.098542e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0974 relative max_delta = 7.198461e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.1045 relative max_delta = 6.437790e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.1045 relative max_delta = 3.793140e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.1045 relative max_delta = 1.328791e-12 Converged to tolerance of 1.328791e-12 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.1045 Final dimensionless free energies f_k = [ 0. -1.10454902] Computing normalized weights... Interval 10, DeltaF=-1.1045 +/- 0.1451, Sum=4.5194 +/- 0.1364 Pairwise MBAR free energy: 4.5194 +/- 0.1364 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4160 N_k = [368 500 487 493 398 335 430 154 166 500 329] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.08446595 2.15045724 2.08621061 1.73768603 1.81069916 1.81560255 1.81614178 1.80203009 1.21127625 0.6431637 ] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.12240805 3.59469325 3.75584809 3.21318815 3.2913119 3.26959441 3.18423745 3.00579167 1.97092991 1.22623062] relative max_delta = 4.445434e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3657 3.9712 4.6113 4.6523 4.8509 4.7857 4.5955 4.2652 3.0187 2.2334 relative max_delta = 3.215109e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.6822 7.5068 11.8002 16.5775 17.8237 17.3661 16.1735 14.3493 11.1723 10.0297 relative max_delta = 7.278375e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6358 8.6813 11.8567 15.5254 16.6390 16.1683 14.5559 12.2731 9.3093 8.1980 relative max_delta = 1.247836e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6977 8.6609 11.8537 15.0880 16.2009 15.7256 14.0880 11.7653 8.8351 7.7225 relative max_delta = 3.134058e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6972 8.6609 11.8489 15.0530 16.1667 15.6914 14.0537 11.7306 8.8008 7.6882 relative max_delta = 2.169537e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6972 8.6609 11.8489 15.0528 16.1665 15.6912 14.0535 11.7304 8.8006 7.6881 relative max_delta = 1.063549e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6972 8.6609 11.8489 15.0528 16.1665 15.6912 14.0535 11.7304 8.8006 7.6881 relative max_delta = 2.625776e-10 Converged to tolerance of 2.625776e-10 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6972 8.6609 11.8489 15.0528 16.1665 15.6912 14.0535 11.7304 8.8006 7.6881 Final dimensionless free energies f_k = [ 0. 6.69715792 8.66091011 11.84885502 15.05278857 16.16652638 15.69119268 14.05348911 11.73041229 8.80063871 7.68806819] Computing normalized weights... DeltaMij: [[ 0. 3.96697674 5.1301805 7.01851932 8.91632882 9.57603732 9.29447941 8.32440643 6.94836127 5.21294697 4.5539299 ] [-3.96697674 0. 1.16320376 3.05154258 4.94935207 5.60906057 5.32750267 4.35742968 2.98138453 1.24597023 0.58695316] [-5.1301805 -1.16320376 0. 1.88833882 3.78614832 4.44585682 4.16429891 3.19422593 1.81818077 0.08276647 -0.5762506 ] [-7.01851932 -3.05154258 -1.88833882 0. 1.8978095 2.55751799 2.27596009 1.3058871 -0.07015805 -1.80557235 -2.46458942] [-8.91632882 -4.94935207 -3.78614832 -1.8978095 0. 0.6597085 0.3781506 -0.59192239 -1.96796755 -3.70338185 -4.36239892] [-9.57603732 -5.60906057 -4.44585682 -2.55751799 -0.6597085 0. -0.2815579 -1.25163089 -2.62767605 -4.36309035 -5.02210742] [-9.29447941 -5.32750267 -4.16429891 -2.27596009 -0.3781506 0.2815579 0. -0.97007299 -2.34611814 -4.08153244 -4.74054951] [-8.32440643 -4.35742968 -3.19422593 -1.3058871 0.59192239 1.25163089 0.97007299 0. -1.37604516 -3.11145946 -3.77047653] [-6.94836127 -2.98138453 -1.81818077 0.07015805 1.96796755 2.62767605 2.34611814 1.37604516 0. -1.7354143 -2.39443137] [-5.21294697 -1.24597023 -0.08276647 1.80557235 3.70338185 4.36309035 4.08153244 3.11145946 1.7354143 0. -0.65901707] [-4.5539299 -0.58695316 0.5762506 2.46458942 4.36239892 5.02210742 4.74054951 3.77047653 2.39443137 0.65901707 0. ]] dDeltaMij: [[ 0. 0.05440907 0.06552459 0.0773631 0.09646383 0.12157533 0.13028615 0.14224818 0.15496103 0.16193106 0.16396038] [ 0.05440907 0. 0.02090466 0.04521117 0.07325728 0.10412463 0.11417468 0.12765548 0.14168379 0.14927507 0.15147403] [ 0.06552459 0.02090466 0. 0.03289351 0.06661508 0.09956328 0.11003075 0.12396301 0.1383662 0.14612992 0.1483755 ] [ 0.0773631 0.04521117 0.03289351 0. 0.05116753 0.0899195 0.10138838 0.11636004 0.13159801 0.13973827 0.14208491] [ 0.09646383 0.07325728 0.06661508 0.05116753 0. 0.06340931 0.07877812 0.09729576 0.11508602 0.12431229 0.1269444 ] [ 0.12157533 0.10412463 0.09956328 0.0899195 0.06340931 0. 0.03091491 0.06452535 0.08915671 0.10078259 0.1040117 ] [ 0.13028615 0.11417468 0.11003075 0.10138838 0.07877812 0.03091491 0. 0.04562315 0.07607999 0.08946424 0.09308814] [ 0.14224818 0.12765548 0.12396301 0.11636004 0.09729576 0.06452535 0.04562315 0. 0.03900202 0.05842188 0.06384423] [ 0.15496103 0.14168379 0.1383662 0.13159801 0.11508602 0.08915671 0.07607999 0.03900202 0. 0.02493427 0.03375559] [ 0.16193106 0.14927507 0.14612992 0.13973827 0.12431229 0.10078259 0.08946424 0.05842188 0.02493427 0. 0.01159834] [ 0.16396038 0.15147403 0.1483755 0.14208491 0.1269444 0.1040117 0.09308814 0.06384423 0.03375559 0.01159834 0. ]] Replica 35 / 40 Computing statistical inefficiencies: lambda 0: g = 1.604 lambda 1: g = 1.544 lambda 2: g = 1.579 lambda 3: g = 1.547 lambda 4: g = 1.682 lambda 5: g = 1.629 lambda 6: g = 1.772 lambda 7: g = 1.697 lambda 8: g = 1.556 lambda 9: g = 1.953 lambda 10: g = 2.430 Subsampling data to produce uncorrelated samples... number of samples per lambda: [459 260 500 418 500 389 500 269 244 300 335] Method: EXP Forward EXP: Interval 1, DeltaF=6.9176 +/- 0.4404, Sum=4.0975 +/- 0.1149 Interval 2, DeltaF=1.8609 +/- 0.2791, Sum=5.1998 +/- 0.1238 Interval 3, DeltaF=3.4634 +/- 0.3757, Sum=7.2513 +/- 0.1494 Interval 4, DeltaF=3.5549 +/- 0.5213, Sum=9.3570 +/- 0.2196 Interval 5, DeltaF=1.7292 +/- 0.4788, Sum=10.3812 +/- 0.2582 Interval 6, DeltaF=-0.3820 +/- 0.3141, Sum=10.1550 +/- 0.2647 Interval 7, DeltaF=-1.4959 +/- 0.2938, Sum=9.2689 +/- 0.2696 Interval 8, DeltaF=-2.3091 +/- 0.3208, Sum=7.9011 +/- 0.2764 Interval 9, DeltaF=-2.7765 +/- 0.3084, Sum=6.2565 +/- 0.2821 Interval 10, DeltaF=-1.0513 +/- 0.1934, Sum=5.6338 +/- 0.2830 Forward EXP free energy: 5.6338 +/- 0.2830 Reverse EXP: Interval 1, DeltaF=7.1831 +/- 0.7538, Sum=4.2548 +/- 0.3366 Interval 2, DeltaF=1.9393 +/- 0.2533, Sum=5.4036 +/- 0.3387 Interval 3, DeltaF=3.0832 +/- 0.3954, Sum=7.2299 +/- 0.3511 Interval 4, DeltaF=3.4231 +/- 0.3602, Sum=9.2575 +/- 0.3595 Interval 5, DeltaF=0.9770 +/- 0.4391, Sum=9.8362 +/- 0.3772 Interval 6, DeltaF=-0.7162 +/- 0.2796, Sum=9.4120 +/- 0.3800 Interval 7, DeltaF=-1.8083 +/- 0.3515, Sum=8.3409 +/- 0.3870 Interval 8, DeltaF=-2.0885 +/- 0.3560, Sum=7.1038 +/- 0.3942 Interval 9, DeltaF=-2.8096 +/- 0.2920, Sum=5.4396 +/- 0.3974 Interval 10, DeltaF=-1.0659 +/- 0.1888, Sum=4.8082 +/- 0.3980 Reverse EXP free energy: 4.8082 +/- 0.3980 Averge of forward and reverse EXP: Interval 1, DeltaF=7.0503 +/- 0.3267, Sum=4.1762 +/- 0.0632 Interval 2, DeltaF=1.9001 +/- 0.0549, Sum=5.3017 +/- 0.0633 Interval 3, DeltaF=3.2733 +/- 0.1146, Sum=7.2406 +/- 0.0637 Interval 4, DeltaF=3.4890 +/- 0.1639, Sum=9.3073 +/- 0.0657 Interval 5, DeltaF=1.3531 +/- 0.1630, Sum=10.1087 +/- 0.0676 Interval 6, DeltaF=-0.5491 +/- 0.0685, Sum=9.7835 +/- 0.0676 Interval 7, DeltaF=-1.6521 +/- 0.0820, Sum=8.8049 +/- 0.0677 Interval 8, DeltaF=-2.1988 +/- 0.0888, Sum=7.5024 +/- 0.0679 Interval 9, DeltaF=-2.7930 +/- 0.0695, Sum=5.8480 +/- 0.0679 Interval 10, DeltaF=-1.0586 +/- 0.0281, Sum=5.2210 +/- 0.0679 Average EXP free energy: 5.2210 +/- 0.0679 Interval 1, DeltaF=7.1831 +/- 0.4373, Sum=4.2548 +/- 0.1133 Interval 2, DeltaF=1.8609 +/- 0.2194, Sum=5.3571 +/- 0.1168 Interval 3, DeltaF=3.0832 +/- 0.6339, Sum=7.1834 +/- 0.2651 Interval 4, DeltaF=3.5549 +/- 0.3451, Sum=9.2891 +/- 0.2744 Interval 5, DeltaF=0.9770 +/- 0.6770, Sum=9.8678 +/- 0.3859 Interval 6, DeltaF=-0.3820 +/- 0.4804, Sum=9.6415 +/- 0.4095 Interval 7, DeltaF=-1.8083 +/- 0.7047, Sum=8.5704 +/- 0.5041 Interval 8, DeltaF=-2.3091 +/- 0.5017, Sum=7.2027 +/- 0.5257 Interval 9, DeltaF=-2.8096 +/- 0.7273, Sum=5.5384 +/- 0.6120 Interval 10, DeltaF=-1.0513 +/- 0.5191, Sum=4.9157 +/- 0.6325 Double-Wide EXP free energy: 4.9157 +/- 0.6325 Method: BAR Interval 1, DeltaF=6.6606 +/- 0.3270, Sum=3.9453 +/- 0.0633 Interval 2, DeltaF=1.9285 +/- 0.2058, Sum=5.0876 +/- 0.0681 Interval 3, DeltaF=3.1868 +/- 0.2582, Sum=6.9753 +/- 0.0787 Interval 4, DeltaF=3.3162 +/- 0.2827, Sum=8.9396 +/- 0.0919 Interval 5, DeltaF=1.1236 +/- 0.3320, Sum=9.6051 +/- 0.1127 Interval 6, DeltaF=-0.6841 +/- 0.2276, Sum=9.1999 +/- 0.1168 Interval 7, DeltaF=-1.7995 +/- 0.2596, Sum=8.1340 +/- 0.1234 Interval 8, DeltaF=-2.2558 +/- 0.2391, Sum=6.7978 +/- 0.1280 Interval 9, DeltaF=-2.7621 +/- 0.2270, Sum=5.1617 +/- 0.1316 Interval 10, DeltaF=-1.0429 +/- 0.1566, Sum=4.5439 +/- 0.1324 BAR free energy: 4.5439 +/- 0.1324 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8892 +/- 0.5779, Sum=4.0807 +/- 0.1978 Interval 2, DeltaF=1.8755 +/- 0.2102, Sum=5.1916 +/- 0.1996 Interval 3, DeltaF=3.2753 +/- 0.3358, Sum=7.1317 +/- 0.2104 Interval 4, DeltaF=3.2038 +/- 0.3568, Sum=9.0295 +/- 0.2235 Interval 5, DeltaF=1.0855 +/- 0.3666, Sum=9.6725 +/- 0.2373 Interval 6, DeltaF=-0.6939 +/- 0.2311, Sum=9.2615 +/- 0.2394 Interval 7, DeltaF=-1.7993 +/- 0.2263, Sum=8.1957 +/- 0.2413 Interval 8, DeltaF=-2.1771 +/- 0.3114, Sum=6.9061 +/- 0.2480 Interval 9, DeltaF=-2.7764 +/- 0.3760, Sum=5.2615 +/- 0.2618 Interval 10, DeltaF=-1.0475 +/- 0.2267, Sum=4.6411 +/- 0.2636 Unopt. BAR free energy: 4.6411 +/- 0.2636 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6600 +/- 0.3241, Sum=3.9449 +/- 0.0622 Interval 2, DeltaF=1.9303 +/- 0.2095, Sum=5.0883 +/- 0.0675 Interval 3, DeltaF=3.1900 +/- 0.2607, Sum=6.9779 +/- 0.0785 Interval 4, DeltaF=3.3064 +/- 0.2904, Sum=8.9364 +/- 0.0931 Interval 5, DeltaF=1.1210 +/- 0.3362, Sum=9.6004 +/- 0.1147 Interval 6, DeltaF=-0.6784 +/- 0.2305, Sum=9.1986 +/- 0.1189 Interval 7, DeltaF=-1.7968 +/- 0.2662, Sum=8.1343 +/- 0.1261 Interval 8, DeltaF=-2.2488 +/- 0.2388, Sum=6.8023 +/- 0.1305 Interval 9, DeltaF=-2.7619 +/- 0.2237, Sum=5.1663 +/- 0.1339 Interval 10, DeltaF=-1.0430 +/- 0.1578, Sum=4.5484 +/- 0.1347 Postopt. BAR free energy: 4.5484 +/- 0.1347 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 719 N_k = [459 260] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.68641995] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.87557239] relative max_delta = 2.439001e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0648 relative max_delta = 3.736127e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.7416 relative max_delta = 2.487206e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6608 relative max_delta = 1.212741e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6606 relative max_delta = 3.171799e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6606 relative max_delta = 2.136189e-10 Converged to tolerance of 2.136189e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6606 Final dimensionless free energies f_k = [ 0. 6.66057712] Computing normalized weights... Interval 1, DeltaF=6.6606 +/- 0.3270, Sum=3.9453 +/- 0.0633 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 760 N_k = [260 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.49475898] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82629369] relative max_delta = 1.815342e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8364 relative max_delta = 5.501720e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9275 relative max_delta = 4.728017e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9285 relative max_delta = 4.767122e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9285 relative max_delta = 5.098275e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.9285 relative max_delta = 2.533112e-15 Converged to tolerance of 2.533112e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9285 Final dimensionless free energies f_k = [ 0. 1.92845044] Computing normalized weights... Interval 2, DeltaF=1.9285 +/- 0.2058, Sum=5.0876 +/- 0.0681 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 918 N_k = [500 418] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53933324] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.33511274] relative max_delta = 3.407885e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4257 relative max_delta = 3.734847e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2285 relative max_delta = 2.486686e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1869 relative max_delta = 1.307834e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1868 relative max_delta = 2.549207e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1868 relative max_delta = 9.931721e-11 Converged to tolerance of 9.931721e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1868 Final dimensionless free energies f_k = [ 0. 3.18678735] Computing normalized weights... Interval 3, DeltaF=3.1868 +/- 0.2582, Sum=6.9753 +/- 0.0787 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 918 N_k = [418 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.01015357] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.7592162] relative max_delta = 4.257934e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9452 relative max_delta = 9.562959e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5504 relative max_delta = 4.521046e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3211 relative max_delta = 6.904788e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3162 relative max_delta = 1.470517e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3162 relative max_delta = 6.997599e-07 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3162 relative max_delta = 1.569489e-13 Converged to tolerance of 1.569489e-13 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3162 Final dimensionless free energies f_k = [ 0. 3.31619166] Computing normalized weights... Interval 4, DeltaF=3.3162 +/- 0.2827, Sum=8.9396 +/- 0.0919 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 889 N_k = [500 389] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.26946382] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.48017048] relative max_delta = 4.388163e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5507 relative max_delta = 1.279948e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.1724 relative max_delta = 5.303179e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.1240 relative max_delta = 4.309831e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.1236 relative max_delta = 3.112882e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.1236 relative max_delta = 1.604939e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.1236 relative max_delta = 6.719040e-15 Converged to tolerance of 6.719040e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.1236 Final dimensionless free energies f_k = [ 0. 1.12360053] Computing normalized weights... Interval 5, DeltaF=1.1236 +/- 0.3320, Sum=9.6051 +/- 0.1127 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 889 N_k = [389 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.44872638] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.59901998] relative max_delta = 2.508991e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.6075 relative max_delta = 1.399163e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.6840 relative max_delta = 1.118575e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.6841 relative max_delta = 1.017041e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.6841 relative max_delta = 1.163632e-10 Converged to tolerance of 1.163632e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.6841 Final dimensionless free energies f_k = [ 0. -0.68410413] Computing normalized weights... Interval 6, DeltaF=-0.6841 +/- 0.2276, Sum=9.1999 +/- 0.1168 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 769 N_k = [500 269] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.07898785] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.48989177] relative max_delta = 2.757945e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.5199 relative max_delta = 1.974562e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.7917 relative max_delta = 1.516843e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.7995 relative max_delta = 4.338217e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.7995 relative max_delta = 3.710604e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.7995 relative max_delta = 2.715149e-12 Converged to tolerance of 2.715149e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.7995 Final dimensionless free energies f_k = [ 0. -1.79948493] Computing normalized weights... Interval 7, DeltaF=-1.7995 +/- 0.2596, Sum=8.1340 +/- 0.1234 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 513 N_k = [269 244] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.6504644] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.07812557] relative max_delta = 2.057918e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0959 relative max_delta = 8.470323e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2556 relative max_delta = 7.082899e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2558 relative max_delta = 5.024845e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2558 relative max_delta = 8.459178e-11 Converged to tolerance of 8.459178e-11 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2558 Final dimensionless free energies f_k = [ 0. -2.25575664] Computing normalized weights... Interval 8, DeltaF=-2.2558 +/- 0.2391, Sum=6.7978 +/- 0.1280 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 544 N_k = [244 300] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.09819641] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.5867415] relative max_delta = 1.888651e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.6045 relative max_delta = 6.802458e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.7635 relative max_delta = 5.756167e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.7621 relative max_delta = 5.114922e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.7621 relative max_delta = 3.235029e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.7621 relative max_delta = 4.823354e-16 Converged to tolerance of 4.823354e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.7621 Final dimensionless free energies f_k = [ 0. -2.76211883] Computing normalized weights... Interval 9, DeltaF=-2.7621 +/- 0.2270, Sum=5.1617 +/- 0.1316 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 635 N_k = [300 335] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.9544884] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.03523266] relative max_delta = 7.799624e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0360 relative max_delta = 7.435436e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0429 relative max_delta = 6.647094e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0429 relative max_delta = 1.329459e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0429 relative max_delta = 5.365175e-14 Converged to tolerance of 5.365175e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0429 Final dimensionless free energies f_k = [ 0. -1.04293407] Computing normalized weights... Interval 10, DeltaF=-1.0429 +/- 0.1566, Sum=4.5439 +/- 0.1324 Pairwise MBAR free energy: 4.5439 +/- 0.1324 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4174 N_k = [459 260 500 418 500 389 500 269 244 300 335] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89184069 1.89863209 1.62840934 1.50552621 1.66896158 1.58049716 1.45147873 1.27202645 0.68751381 0.36254409] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.74093085 3.10421765 2.98914485 2.80712371 3.00999234 2.85292315 2.57081167 2.15576718 1.14490228 0.63805023] relative max_delta = 4.383505e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.9841 3.4736 3.8176 4.1492 4.4598 4.2517 3.8547 3.2858 2.0869 1.5243 relative max_delta = 3.250798e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.3348 6.9870 11.0309 15.6764 16.9188 16.2538 14.7749 12.7469 9.8484 8.7909 relative max_delta = 7.364017e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.5989 8.5721 11.6986 15.2830 16.4015 15.7255 13.9651 11.7188 8.9264 7.8887 relative max_delta = 9.664384e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6851 8.6058 11.7467 15.0624 16.1792 15.5007 13.7345 11.4789 8.6945 7.6564 relative max_delta = 1.482462e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6843 8.6059 11.7442 15.0514 16.1685 15.4900 13.7238 11.4682 8.6838 7.6457 relative max_delta = 6.781501e-04 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6843 8.6059 11.7442 15.0514 16.1685 15.4900 13.7238 11.4682 8.6838 7.6456 relative max_delta = 8.113530e-07 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6843 8.6059 11.7442 15.0514 16.1685 15.4900 13.7238 11.4682 8.6838 7.6456 relative max_delta = 1.232798e-12 Converged to tolerance of 1.232798e-12 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6843 8.6059 11.7442 15.0514 16.1685 15.4900 13.7238 11.4682 8.6838 7.6456 Final dimensionless free energies f_k = [ 0. 6.6843405 8.60587779 11.74424013 15.05143216 16.16850127 15.48998002 13.72378281 11.46816389 8.68382934 7.64564731] Computing normalized weights... DeltaMij: [[ 0. 3.95938451 5.0975828 6.95655201 8.91552536 9.57720712 9.17529364 8.12910907 6.79302175 5.14375641 4.52880243] [-3.95938451 0. 1.13819829 2.99716751 4.95614086 5.61782261 5.21590913 4.16972457 2.83363724 1.18437191 0.56941792] [-5.0975828 -1.13819829 0. 1.85896921 3.81794256 4.47962432 4.07771084 3.03152627 1.69543895 0.04617361 -0.56878037] [-6.95655201 -2.99716751 -1.85896921 0. 1.95897335 2.6206551 2.21874163 1.17255706 -0.16353027 -1.8127956 -2.42774958] [-8.91552536 -4.95614086 -3.81794256 -1.95897335 0. 0.66168175 0.25976828 -0.78641629 -2.12250362 -3.77176895 -4.38672293] [-9.57720712 -5.61782261 -4.47962432 -2.6206551 -0.66168175 0. -0.40191347 -1.44809804 -2.78418537 -4.4334507 -5.04840468] [-9.17529364 -5.21590913 -4.07771084 -2.21874163 -0.25976828 0.40191347 0. -1.04618457 -2.38227189 -4.03153723 -4.64649121] [-8.12910907 -4.16972457 -3.03152627 -1.17255706 0.78641629 1.44809804 1.04618457 0. -1.33608732 -2.98535266 -3.60030664] [-6.79302175 -2.83363724 -1.69543895 0.16353027 2.12250362 2.78418537 2.38227189 1.33608732 0. -1.64926533 -2.26421932] [-5.14375641 -1.18437191 -0.04617361 1.8127956 3.77176895 4.4334507 4.03153723 2.98535266 1.64926533 0. -0.61495398] [-4.52880243 -0.56941792 0.56878037 2.42774958 4.38672293 5.04840468 4.64649121 3.60030664 2.26421932 0.61495398 0. ]] dDeltaMij: [[ 0. 0.05941628 0.0739918 0.08670361 0.10210043 0.12451904 0.13249292 0.14112879 0.14900806 0.15493999 0.15744622] [ 0.05941628 0. 0.0238229 0.04980402 0.0734307 0.10233574 0.11190167 0.12200387 0.13103821 0.13774618 0.14055933] [ 0.0739918 0.0238229 0. 0.03621977 0.06519678 0.09659788 0.10667957 0.11723264 0.12660789 0.1335386 0.13643852] [ 0.08670361 0.04980402 0.03621977 0. 0.04623546 0.08491097 0.09622577 0.10780701 0.11793396 0.1253452 0.12843026] [ 0.10210043 0.0734307 0.06519678 0.04623546 0. 0.06253493 0.07716575 0.0912021 0.10297504 0.11138609 0.11484675] [ 0.12451904 0.10233574 0.09659788 0.08491097 0.06253493 0. 0.02961882 0.0565366 0.07407604 0.08538016 0.08984792] [ 0.13249292 0.11190167 0.10667957 0.09622577 0.07716575 0.02961882 0. 0.03739421 0.06023378 0.07374172 0.07887332] [ 0.14112879 0.12200387 0.11723264 0.10780701 0.0912021 0.0565366 0.03739421 0. 0.03052778 0.05033567 0.05761453] [ 0.14900806 0.13103821 0.12660789 0.11793396 0.10297504 0.07407604 0.06023378 0.03052778 0. 0.02482437 0.03539108] [ 0.15493999 0.13774618 0.1335386 0.1253452 0.11138609 0.08538016 0.07374172 0.05033567 0.02482437 0. 0.01321219] [ 0.15744622 0.14055933 0.13643852 0.12843026 0.11484675 0.08984792 0.07887332 0.05761453 0.03539108 0.01321219 0. ]] Replica 36 / 40 Computing statistical inefficiencies: lambda 0: g = 1.377 lambda 1: g = 1.806 lambda 2: g = 2.083 lambda 3: g = 2.849 lambda 4: g = 1.987 lambda 5: g = 1.482 lambda 6: g = 1.282 lambda 7: g = 2.078 lambda 8: g = 3.901 lambda 9: g = 1.000 lambda 10: g = 1.922 Subsampling data to produce uncorrelated samples... number of samples per lambda: [378 500 390 500 500 396 316 230 500 327 447] Method: EXP Forward EXP: Interval 1, DeltaF=6.4470 +/- 0.6057, Sum=3.8188 +/- 0.2173 Interval 2, DeltaF=1.8618 +/- 0.2601, Sum=4.9216 +/- 0.2210 Interval 3, DeltaF=3.1793 +/- 0.4356, Sum=6.8049 +/- 0.2479 Interval 4, DeltaF=4.3076 +/- 0.3140, Sum=9.3564 +/- 0.2547 Interval 5, DeltaF=2.0236 +/- 0.4655, Sum=10.5551 +/- 0.2852 Interval 6, DeltaF=-0.6124 +/- 0.5616, Sum=10.1924 +/- 0.3410 Interval 7, DeltaF=-2.1969 +/- 0.5923, Sum=8.8911 +/- 0.3993 Interval 8, DeltaF=-2.4536 +/- 0.3855, Sum=7.4377 +/- 0.4089 Interval 9, DeltaF=-2.8915 +/- 0.2351, Sum=5.7250 +/- 0.4102 Interval 10, DeltaF=-1.1005 +/- 0.1847, Sum=5.0731 +/- 0.4107 Forward EXP free energy: 5.0731 +/- 0.4107 Reverse EXP: Interval 1, DeltaF=6.8391 +/- 0.4818, Sum=4.0510 +/- 0.1375 Interval 2, DeltaF=1.9540 +/- 0.2749, Sum=5.2084 +/- 0.1446 Interval 3, DeltaF=3.1230 +/- 0.3509, Sum=7.0583 +/- 0.1619 Interval 4, DeltaF=3.5802 +/- 0.3745, Sum=9.1790 +/- 0.1820 Interval 5, DeltaF=1.5122 +/- 0.4514, Sum=10.0747 +/- 0.2184 Interval 6, DeltaF=-0.5361 +/- 0.3073, Sum=9.7571 +/- 0.2254 Interval 7, DeltaF=-1.6540 +/- 0.3970, Sum=8.7774 +/- 0.2440 Interval 8, DeltaF=-2.2985 +/- 0.2868, Sum=7.4159 +/- 0.2488 Interval 9, DeltaF=-3.0303 +/- 0.2799, Sum=5.6210 +/- 0.2531 Interval 10, DeltaF=-1.0820 +/- 0.1822, Sum=4.9801 +/- 0.2539 Reverse EXP free energy: 4.9801 +/- 0.2539 Averge of forward and reverse EXP: Interval 1, DeltaF=6.6430 +/- 0.2363, Sum=3.9349 +/- 0.0331 Interval 2, DeltaF=1.9079 +/- 0.0552, Sum=5.0650 +/- 0.0331 Interval 3, DeltaF=3.1512 +/- 0.1231, Sum=6.9316 +/- 0.0343 Interval 4, DeltaF=3.9439 +/- 0.0933, Sum=9.2677 +/- 0.0347 Interval 5, DeltaF=1.7679 +/- 0.1619, Sum=10.3149 +/- 0.0380 Interval 6, DeltaF=-0.5742 +/- 0.1792, Sum=9.9747 +/- 0.0425 Interval 7, DeltaF=-1.9254 +/- 0.2093, Sum=8.8342 +/- 0.0498 Interval 8, DeltaF=-2.3761 +/- 0.0924, Sum=7.4268 +/- 0.0501 Interval 9, DeltaF=-2.9609 +/- 0.0522, Sum=5.6730 +/- 0.0501 Interval 10, DeltaF=-1.0912 +/- 0.0259, Sum=5.0266 +/- 0.0501 Average EXP free energy: 5.0266 +/- 0.0501 Interval 1, DeltaF=6.8391 +/- 0.1786, Sum=4.0510 +/- 0.0189 Interval 2, DeltaF=1.8618 +/- 0.4027, Sum=5.1539 +/- 0.0979 Interval 3, DeltaF=3.1230 +/- 0.2821, Sum=7.0037 +/- 0.1087 Interval 4, DeltaF=4.3076 +/- 0.4618, Sum=9.5553 +/- 0.1666 Interval 5, DeltaF=1.5122 +/- 0.3693, Sum=10.4510 +/- 0.1852 Interval 6, DeltaF=-0.6124 +/- 0.5776, Sum=10.0883 +/- 0.2708 Interval 7, DeltaF=-1.6540 +/- 0.4316, Sum=9.1085 +/- 0.2925 Interval 8, DeltaF=-2.4536 +/- 0.7426, Sum=7.6552 +/- 0.4385 Interval 9, DeltaF=-3.0303 +/- 0.4611, Sum=5.8602 +/- 0.4562 Interval 10, DeltaF=-1.1005 +/- 0.7543, Sum=5.2084 +/- 0.5672 Double-Wide EXP free energy: 5.2084 +/- 0.5672 Method: BAR Interval 1, DeltaF=6.7809 +/- 0.3089, Sum=4.0166 +/- 0.0565 Interval 2, DeltaF=1.9375 +/- 0.1981, Sum=5.1643 +/- 0.0611 Interval 3, DeltaF=3.2205 +/- 0.2570, Sum=7.0719 +/- 0.0726 Interval 4, DeltaF=3.4360 +/- 0.2778, Sum=9.1071 +/- 0.0858 Interval 5, DeltaF=1.3064 +/- 0.3188, Sum=9.8809 +/- 0.1048 Interval 6, DeltaF=-0.4857 +/- 0.2397, Sum=9.5933 +/- 0.1102 Interval 7, DeltaF=-1.6660 +/- 0.2792, Sum=8.6064 +/- 0.1195 Interval 8, DeltaF=-2.3126 +/- 0.2309, Sum=7.2366 +/- 0.1236 Interval 9, DeltaF=-2.9284 +/- 0.1965, Sum=5.5020 +/- 0.1257 Interval 10, DeltaF=-1.0960 +/- 0.1474, Sum=4.8528 +/- 0.1263 BAR free energy: 4.8528 +/- 0.1263 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.4635 +/- 0.4224, Sum=3.8286 +/- 0.1057 Interval 2, DeltaF=1.8902 +/- 0.2809, Sum=4.9482 +/- 0.1156 Interval 3, DeltaF=3.1620 +/- 0.3065, Sum=6.8212 +/- 0.1283 Interval 4, DeltaF=3.6508 +/- 0.3677, Sum=8.9837 +/- 0.1512 Interval 5, DeltaF=1.3173 +/- 0.3556, Sum=9.7640 +/- 0.1688 Interval 6, DeltaF=-0.4975 +/- 0.2297, Sum=9.4693 +/- 0.1716 Interval 7, DeltaF=-1.6660 +/- 0.2645, Sum=8.4824 +/- 0.1766 Interval 8, DeltaF=-2.3008 +/- 0.3632, Sum=7.1196 +/- 0.1931 Interval 9, DeltaF=-2.9771 +/- 0.2948, Sum=5.3562 +/- 0.1998 Interval 10, DeltaF=-1.0905 +/- 0.2349, Sum=4.7102 +/- 0.2025 Unopt. BAR free energy: 4.7102 +/- 0.2025 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7954 +/- 0.3108, Sum=4.0252 +/- 0.0572 Interval 2, DeltaF=1.9393 +/- 0.1975, Sum=5.1739 +/- 0.0617 Interval 3, DeltaF=3.2206 +/- 0.2567, Sum=7.0816 +/- 0.0730 Interval 4, DeltaF=3.4437 +/- 0.2893, Sum=9.1214 +/- 0.0882 Interval 5, DeltaF=1.3077 +/- 0.3282, Sum=9.8960 +/- 0.1089 Interval 6, DeltaF=-0.4975 +/- 0.2297, Sum=9.6013 +/- 0.1133 Interval 7, DeltaF=-1.6766 +/- 0.2882, Sum=8.6082 +/- 0.1235 Interval 8, DeltaF=-2.3112 +/- 0.2437, Sum=7.2392 +/- 0.1284 Interval 9, DeltaF=-2.9274 +/- 0.1983, Sum=5.5053 +/- 0.1305 Interval 10, DeltaF=-1.0956 +/- 0.1538, Sum=4.8563 +/- 0.1313 Postopt. BAR free energy: 4.8563 +/- 0.1313 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 878 N_k = [378 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.39454116] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.70438641] relative max_delta = 2.784306e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9015 relative max_delta = 4.021791e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6873 relative max_delta = 2.670358e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7806 relative max_delta = 1.376480e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7809 relative max_delta = 4.636972e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7809 relative max_delta = 5.253948e-10 Converged to tolerance of 5.253948e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7809 Final dimensionless free energies f_k = [ 0. 6.78089793] Computing normalized weights... Interval 1, DeltaF=6.7809 +/- 0.3089, Sum=4.0166 +/- 0.0565 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 890 N_k = [500 390] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53158934] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.83794779] relative max_delta = 1.666851e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8479 relative max_delta = 5.408175e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9378 relative max_delta = 4.637932e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9375 relative max_delta = 1.379540e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9375 relative max_delta = 9.496250e-10 Converged to tolerance of 9.496250e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9375 Final dimensionless free energies f_k = [ 0. 1.9375491] Computing normalized weights... Interval 2, DeltaF=1.9375 +/- 0.1981, Sum=5.1643 +/- 0.0611 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 890 N_k = [390 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.63671313] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.43369803] relative max_delta = 3.274790e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5131 relative max_delta = 3.160535e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2254 relative max_delta = 2.208356e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2205 relative max_delta = 1.535545e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2205 relative max_delta = 7.924718e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2205 relative max_delta = 2.757918e-16 Converged to tolerance of 2.757918e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2205 Final dimensionless free energies f_k = [ 0. 3.22046725] Computing normalized weights... Interval 3, DeltaF=3.2205 +/- 0.2570, Sum=7.0719 +/- 0.0726 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.0230227] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.79551878] relative max_delta = 4.302356e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9976 relative max_delta = 1.011767e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7240 relative max_delta = 4.635721e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4441 relative max_delta = 8.125482e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4360 relative max_delta = 2.367381e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4360 relative max_delta = 2.074196e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4360 relative max_delta = 1.594396e-12 Converged to tolerance of 1.594396e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4360 Final dimensionless free energies f_k = [ 0. 3.4359622] Computing normalized weights... Interval 4, DeltaF=3.4360 +/- 0.2778, Sum=9.1071 +/- 0.0858 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 896 N_k = [500 396] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.3479668] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.61141905] relative max_delta = 4.308866e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6875 relative max_delta = 1.107179e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.3590 relative max_delta = 4.940974e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3068 relative max_delta = 4.000713e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3064 relative max_delta = 2.877208e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3064 relative max_delta = 1.471355e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3064 relative max_delta = 1.359750e-15 Converged to tolerance of 1.359750e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3064 Final dimensionless free energies f_k = [ 0. 1.30638524] Computing normalized weights... Interval 5, DeltaF=1.3064 +/- 0.3188, Sum=9.8809 +/- 0.1048 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 712 N_k = [396 316] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.31473177] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.42376737] relative max_delta = 2.573006e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4299 relative max_delta = 1.432526e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.4854 relative max_delta = 1.143061e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.4857 relative max_delta = 5.099209e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.4857 relative max_delta = 1.050076e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.4857 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.4857 Final dimensionless free energies f_k = [ 0. -0.48565937] Computing normalized weights... Interval 6, DeltaF=-0.4857 +/- 0.2397, Sum=9.5933 +/- 0.1102 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 546 N_k = [316 230] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00050916] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.37883198] relative max_delta = 2.743792e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4070 relative max_delta = 2.000436e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6613 relative max_delta = 1.530793e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6660 relative max_delta = 2.838189e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6660 relative max_delta = 1.071908e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6660 relative max_delta = 1.532706e-13 Converged to tolerance of 1.532706e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6660 Final dimensionless free energies f_k = [ 0. -1.66601638] Computing normalized weights... Interval 7, DeltaF=-1.6660 +/- 0.2792, Sum=8.6064 +/- 0.1195 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 730 N_k = [230 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.76084757] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.14845133] relative max_delta = 1.804108e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1652 relative max_delta = 7.720269e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3150 relative max_delta = 6.472308e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3126 relative max_delta = 1.044849e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3126 relative max_delta = 2.582176e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3126 relative max_delta = 1.939519e-14 Converged to tolerance of 1.939519e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3126 Final dimensionless free energies f_k = [ 0. -2.3125841] Computing normalized weights... Interval 8, DeltaF=-2.3126 +/- 0.2309, Sum=7.2366 +/- 0.1236 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 827 N_k = [500 327] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.20643155] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.75487591] relative max_delta = 1.990813e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7721 relative max_delta = 6.216068e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9274 relative max_delta = 5.304014e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9284 relative max_delta = 3.361463e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9284 relative max_delta = 1.788186e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9284 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9284 Final dimensionless free energies f_k = [ 0. -2.92836036] Computing normalized weights... Interval 9, DeltaF=-2.9284 +/- 0.1965, Sum=5.5020 +/- 0.1257 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 774 N_k = [327 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01311567] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.08922985] relative max_delta = 6.987889e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0899 relative max_delta = 6.214820e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0960 relative max_delta = 5.561666e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0960 relative max_delta = 2.383758e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0960 relative max_delta = 4.355801e-13 Converged to tolerance of 4.355801e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0960 Final dimensionless free energies f_k = [ 0. -1.09600019] Computing normalized weights... Interval 10, DeltaF=-1.0960 +/- 0.1474, Sum=4.8528 +/- 0.1263 Pairwise MBAR free energy: 4.8528 +/- 0.1263 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4484 N_k = [378 500 390 500 500 396 316 230 500 327 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.00047156 1.9907847 1.85483821 1.70770135 1.85512769 1.9310267 1.97741998 1.83649547 0.98488208 0.51247401] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.99772 3.3480218 3.36712884 3.16187943 3.41407564 3.49720141 3.46441482 3.05221575 1.61463824 0.93149954] relative max_delta = 4.478366e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2546 3.7410 4.2145 4.5933 4.9719 5.0062 4.8568 4.2609 2.6450 1.9198 relative max_delta = 3.111696e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.7157 7.4694 11.6067 16.6891 18.1565 17.7414 16.4771 14.1816 11.0213 9.9259 relative max_delta = 7.261661e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7462 8.7628 11.9712 15.7941 17.1038 16.6153 14.9862 12.6458 9.7107 8.6167 relative max_delta = 8.979319e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7931 8.7207 11.9367 15.3952 16.6998 16.2057 14.5666 12.2261 9.2933 8.2009 relative max_delta = 2.512887e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7925 8.7207 11.9324 15.3726 16.6777 16.1835 14.5445 12.2040 9.2711 8.1787 relative max_delta = 1.359884e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7925 8.7207 11.9324 15.3725 16.6776 16.1834 14.5444 12.2039 9.2711 8.1787 relative max_delta = 3.650343e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7925 8.7207 11.9324 15.3725 16.6776 16.1834 14.5444 12.2039 9.2711 8.1787 relative max_delta = 2.724051e-11 Converged to tolerance of 2.724051e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7925 8.7207 11.9324 15.3725 16.6776 16.1834 14.5444 12.2039 9.2711 8.1787 Final dimensionless free energies f_k = [ 0. 6.79247289 8.72072152 11.93241913 15.37249659 16.67761709 16.1834306 14.54441808 12.2039065 9.27108173 8.17868754] Computing normalized weights... DeltaMij: [[ 0. 4.02343536 5.16560903 7.06801746 9.10570382 9.87877543 9.58605031 8.61520199 7.22882957 5.49160794 4.84454206] [-4.02343536 0. 1.14217368 3.04458211 5.08226846 5.85534007 5.56261496 4.59176663 3.20539422 1.46817258 0.82110671] [-5.16560903 -1.14217368 0. 1.90240843 3.94009478 4.7131664 4.42044128 3.44959296 2.06322054 0.32599891 -0.32106697] [-7.06801746 -3.04458211 -1.90240843 0. 2.03768635 2.81075796 2.51803285 1.54718452 0.16081211 -1.57640953 -2.2234754 ] [-9.10570382 -5.08226846 -3.94009478 -2.03768635 0. 0.77307161 0.4803465 -0.49050183 -1.87687424 -3.61409588 -4.26116175] [-9.87877543 -5.85534007 -4.7131664 -2.81075796 -0.77307161 0. -0.29272512 -1.26357344 -2.64994586 -4.38716749 -5.03423337] [-9.58605031 -5.56261496 -4.42044128 -2.51803285 -0.4803465 0.29272512 0. -0.97084832 -2.35722074 -4.09444237 -4.74150825] [-8.61520199 -4.59176663 -3.44959296 -1.54718452 0.49050183 1.26357344 0.97084832 0. -1.38637242 -3.12359405 -3.77065993] [-7.22882957 -3.20539422 -2.06322054 -0.16081211 1.87687424 2.64994586 2.35722074 1.38637242 0. -1.73722163 -2.38428751] [-5.49160794 -1.46817258 -0.32599891 1.57640953 3.61409588 4.38716749 4.09444237 3.12359405 1.73722163 0. -0.64706588] [-4.84454206 -0.82110671 0.32106697 2.2234754 4.26116175 5.03423337 4.74150825 3.77065993 2.38428751 0.64706588 0. ]] dDeltaMij: [[ 0. 0.05517783 0.06694335 0.07934696 0.09403735 0.11558284 0.12491393 0.13685065 0.14521381 0.14930184 0.15097307] [ 0.05517783 0. 0.02178226 0.04699666 0.06902657 0.09633944 0.10735633 0.12103715 0.13041834 0.13495529 0.13680189] [ 0.06694335 0.02178226 0. 0.03420641 0.06141281 0.09104131 0.1026285 0.11686411 0.12655501 0.1312256 0.13312395] [ 0.07934696 0.04699666 0.03420641 0. 0.04423976 0.08041501 0.09333173 0.10879067 0.11914009 0.12409009 0.1260959 ] [ 0.09403735 0.06902657 0.06141281 0.04423976 0. 0.05806202 0.07489257 0.09345614 0.10532313 0.11089162 0.11313169] [ 0.11558284 0.09633944 0.09104131 0.08041501 0.05806202 0. 0.03279059 0.06431591 0.08062737 0.08777511 0.09058854] [ 0.12491393 0.10735633 0.1026285 0.09333173 0.07489257 0.03279059 0. 0.04195322 0.0634635 0.0723713 0.07575895] [ 0.13685065 0.12103715 0.11686411 0.10879067 0.09345614 0.06431591 0.04195322 0. 0.02952273 0.04407168 0.04952267] [ 0.14521381 0.13041834 0.12655501 0.11914009 0.10532313 0.08062737 0.0634635 0.02952273 0. 0.01957247 0.02836296] [ 0.14930184 0.13495529 0.1312256 0.12409009 0.11089162 0.08777511 0.0723713 0.04407168 0.01957247 0. 0.01107989] [ 0.15097307 0.13680189 0.13312395 0.1260959 0.11313169 0.09058854 0.07575895 0.04952267 0.02836296 0.01107989 0. ]] Replica 37 / 40 Computing statistical inefficiencies: lambda 0: g = 1.777 lambda 1: g = 1.892 lambda 2: g = 2.119 lambda 3: g = 2.092 lambda 4: g = 2.213 lambda 5: g = 1.803 lambda 6: g = 1.782 lambda 7: g = 1.000 lambda 8: g = 1.807 lambda 9: g = 1.720 lambda 10: g = 1.897 Subsampling data to produce uncorrelated samples... number of samples per lambda: [478 315 500 500 331 341 500 164 336 217 380] Method: EXP Forward EXP: Interval 1, DeltaF=6.8348 +/- 0.4517, Sum=4.0485 +/- 0.1209 Interval 2, DeltaF=2.0288 +/- 0.2855, Sum=5.2502 +/- 0.1301 Interval 3, DeltaF=3.5877 +/- 0.3795, Sum=7.3753 +/- 0.1556 Interval 4, DeltaF=3.4910 +/- 0.4315, Sum=9.4432 +/- 0.1907 Interval 5, DeltaF=1.9864 +/- 0.4366, Sum=10.6198 +/- 0.2217 Interval 6, DeltaF=-0.2124 +/- 0.3200, Sum=10.4940 +/- 0.2298 Interval 7, DeltaF=-1.5472 +/- 0.4395, Sum=9.5775 +/- 0.2567 Interval 8, DeltaF=-2.2041 +/- 0.3398, Sum=8.2719 +/- 0.2657 Interval 9, DeltaF=-2.8898 +/- 0.2551, Sum=6.5602 +/- 0.2684 Interval 10, DeltaF=-1.0921 +/- 0.2074, Sum=5.9133 +/- 0.2697 Forward EXP free energy: 5.9133 +/- 0.2697 Reverse EXP: Interval 1, DeltaF=6.7630 +/- 0.5176, Sum=4.0060 +/- 0.1587 Interval 2, DeltaF=2.1004 +/- 0.2811, Sum=5.2502 +/- 0.1654 Interval 3, DeltaF=3.2052 +/- 0.4315, Sum=7.1487 +/- 0.1988 Interval 4, DeltaF=3.4983 +/- 0.4002, Sum=9.2209 +/- 0.2203 Interval 5, DeltaF=1.2678 +/- 0.4761, Sum=9.9719 +/- 0.2580 Interval 6, DeltaF=-0.5912 +/- 0.2808, Sum=9.6217 +/- 0.2622 Interval 7, DeltaF=-1.6481 +/- 0.3943, Sum=8.6455 +/- 0.2779 Interval 8, DeltaF=-2.4791 +/- 0.2874, Sum=7.1770 +/- 0.2822 Interval 9, DeltaF=-3.0955 +/- 0.2835, Sum=5.3434 +/- 0.2862 Interval 10, DeltaF=-1.0582 +/- 0.1829, Sum=4.7166 +/- 0.2868 Reverse EXP free energy: 4.7166 +/- 0.2868 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7989 +/- 0.1833, Sum=4.0272 +/- 0.0199 Interval 2, DeltaF=2.0646 +/- 0.0618, Sum=5.2502 +/- 0.0200 Interval 3, DeltaF=3.3964 +/- 0.1281, Sum=7.2620 +/- 0.0223 Interval 4, DeltaF=3.4947 +/- 0.1337, Sum=9.3321 +/- 0.0246 Interval 5, DeltaF=1.6271 +/- 0.1612, Sum=10.2958 +/- 0.0291 Interval 6, DeltaF=-0.4018 +/- 0.0703, Sum=10.0578 +/- 0.0292 Interval 7, DeltaF=-1.5977 +/- 0.1350, Sum=9.1115 +/- 0.0311 Interval 8, DeltaF=-2.3416 +/- 0.0773, Sum=7.7245 +/- 0.0313 Interval 9, DeltaF=-2.9927 +/- 0.0563, Sum=5.9518 +/- 0.0314 Interval 10, DeltaF=-1.0751 +/- 0.0296, Sum=5.3150 +/- 0.0314 Average EXP free energy: 5.3150 +/- 0.0314 Interval 1, DeltaF=6.7630 +/- 0.2062, Sum=4.0060 +/- 0.0252 Interval 2, DeltaF=2.0288 +/- 0.2308, Sum=5.2077 +/- 0.0404 Interval 3, DeltaF=3.2052 +/- 0.3361, Sum=7.1063 +/- 0.0781 Interval 4, DeltaF=3.4910 +/- 0.3198, Sum=9.1742 +/- 0.0989 Interval 5, DeltaF=1.2678 +/- 0.4408, Sum=9.9251 +/- 0.1517 Interval 6, DeltaF=-0.2124 +/- 0.4148, Sum=9.7993 +/- 0.1828 Interval 7, DeltaF=-1.6481 +/- 0.4964, Sum=8.8231 +/- 0.2339 Interval 8, DeltaF=-2.2041 +/- 0.4800, Sum=7.5175 +/- 0.2708 Interval 9, DeltaF=-3.0955 +/- 0.5222, Sum=5.6839 +/- 0.3153 Interval 10, DeltaF=-1.0921 +/- 0.4944, Sum=5.0370 +/- 0.3470 Double-Wide EXP free energy: 5.0370 +/- 0.3470 Method: BAR Interval 1, DeltaF=6.9019 +/- 0.3120, Sum=4.0883 +/- 0.0577 Interval 2, DeltaF=2.0585 +/- 0.2088, Sum=5.3076 +/- 0.0632 Interval 3, DeltaF=3.2384 +/- 0.2469, Sum=7.2258 +/- 0.0728 Interval 4, DeltaF=3.3079 +/- 0.3051, Sum=9.1852 +/- 0.0913 Interval 5, DeltaF=1.2276 +/- 0.3328, Sum=9.9123 +/- 0.1125 Interval 6, DeltaF=-0.5558 +/- 0.2313, Sum=9.5831 +/- 0.1168 Interval 7, DeltaF=-1.6323 +/- 0.2750, Sum=8.6162 +/- 0.1251 Interval 8, DeltaF=-2.3472 +/- 0.2504, Sum=7.2259 +/- 0.1305 Interval 9, DeltaF=-2.9377 +/- 0.2152, Sum=5.4858 +/- 0.1334 Interval 10, DeltaF=-1.0689 +/- 0.1538, Sum=4.8526 +/- 0.1341 BAR free energy: 4.8526 +/- 0.1341 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.8133 +/- 0.5638, Sum=4.0358 +/- 0.1883 Interval 2, DeltaF=2.0352 +/- 0.2337, Sum=5.2413 +/- 0.1910 Interval 3, DeltaF=3.4002 +/- 0.3228, Sum=7.2553 +/- 0.2008 Interval 4, DeltaF=3.0121 +/- 0.4153, Sum=9.0395 +/- 0.2253 Interval 5, DeltaF=1.2198 +/- 0.3646, Sum=9.7620 +/- 0.2386 Interval 6, DeltaF=-0.5684 +/- 0.2357, Sum=9.4254 +/- 0.2409 Interval 7, DeltaF=-1.6447 +/- 0.1776, Sum=8.4512 +/- 0.2416 Interval 8, DeltaF=-2.4251 +/- 0.3967, Sum=7.0147 +/- 0.2590 Interval 9, DeltaF=-3.0229 +/- 0.3242, Sum=5.2241 +/- 0.2664 Interval 10, DeltaF=-1.0640 +/- 0.2670, Sum=4.5939 +/- 0.2697 Unopt. BAR free energy: 4.5939 +/- 0.2697 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.9063 +/- 0.3117, Sum=4.0908 +/- 0.0576 Interval 2, DeltaF=2.0576 +/- 0.2070, Sum=5.3097 +/- 0.0629 Interval 3, DeltaF=3.2486 +/- 0.2487, Sum=7.2339 +/- 0.0728 Interval 4, DeltaF=3.2809 +/- 0.3170, Sum=9.1774 +/- 0.0940 Interval 5, DeltaF=1.2264 +/- 0.3387, Sum=9.9038 +/- 0.1160 Interval 6, DeltaF=-0.5432 +/- 0.2337, Sum=9.5821 +/- 0.1204 Interval 7, DeltaF=-1.6270 +/- 0.2970, Sum=8.6183 +/- 0.1313 Interval 8, DeltaF=-2.3559 +/- 0.2660, Sum=7.2228 +/- 0.1378 Interval 9, DeltaF=-2.9366 +/- 0.2170, Sum=5.4834 +/- 0.1406 Interval 10, DeltaF=-1.0685 +/- 0.1625, Sum=4.8505 +/- 0.1415 Postopt. BAR free energy: 4.8505 +/- 0.1415 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 793 N_k = [478 315] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.80645643] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 5.09095421] relative max_delta = 2.523098e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.2816 relative max_delta = 3.609551e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.9711 relative max_delta = 2.423615e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.9020 relative max_delta = 1.001999e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.9019 relative max_delta = 9.751057e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.9019 relative max_delta = 9.474763e-12 Converged to tolerance of 9.474763e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.9019 Final dimensionless free energies f_k = [ 0. 6.90190476] Computing normalized weights... Interval 1, DeltaF=6.9019 +/- 0.3120, Sum=4.0883 +/- 0.0577 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 815 N_k = [315 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.55153559] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.92288355] relative max_delta = 1.931204e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9363 relative max_delta = 6.935506e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 2.0574 relative max_delta = 5.886063e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 2.0585 relative max_delta = 5.346401e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 2.0585 relative max_delta = 4.870065e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 2.0585 relative max_delta = 3.235993e-15 Converged to tolerance of 3.235993e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 2.0585 Final dimensionless free energies f_k = [ 0. 2.05851418] Computing normalized weights... Interval 2, DeltaF=2.0585 +/- 0.2088, Sum=5.3076 +/- 0.0632 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.58959212] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.41618406] relative max_delta = 3.421064e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5023 relative max_delta = 3.439788e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2673 relative max_delta = 2.341431e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2384 relative max_delta = 8.917158e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2384 relative max_delta = 5.362014e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2384 relative max_delta = 2.050559e-12 Converged to tolerance of 2.050559e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2384 Final dimensionless free energies f_k = [ 0. 3.23836916] Computing normalized weights... Interval 3, DeltaF=3.2384 +/- 0.2469, Sum=7.2258 +/- 0.0728 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 831 N_k = [500 331] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.87420917] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.56226241] relative max_delta = 4.404210e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.7949 relative max_delta = 1.295996e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.7421 relative max_delta = 5.203564e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3349 relative max_delta = 1.221141e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3080 relative max_delta = 8.130824e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3079 relative max_delta = 3.479167e-05 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3079 relative max_delta = 6.351767e-10 Converged to tolerance of 6.351767e-10 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3079 Final dimensionless free energies f_k = [ 0. 3.30786041] Computing normalized weights... Interval 4, DeltaF=3.3079 +/- 0.3051, Sum=9.1852 +/- 0.0913 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 672 N_k = [331 341] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.3560988] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.61720529] relative max_delta = 4.230464e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6824 relative max_delta = 9.550888e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2604 relative max_delta = 4.585853e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2277 relative max_delta = 2.659482e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2276 relative max_delta = 8.907710e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2276 relative max_delta = 9.979018e-10 Converged to tolerance of 9.979018e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2276 Final dimensionless free energies f_k = [ 0. 1.22760184] Computing normalized weights... Interval 5, DeltaF=1.2276 +/- 0.3328, Sum=9.9123 +/- 0.1125 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 841 N_k = [341 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.36438721] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.48698695] relative max_delta = 2.517516e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4939 relative max_delta = 1.394431e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 1.114967e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 2.559878e-05 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 5.892323e-14 Converged to tolerance of 5.892323e-14 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5558 Final dimensionless free energies f_k = [ 0. -0.55583477] Computing normalized weights... Interval 6, DeltaF=-0.5558 +/- 0.2313, Sum=9.5831 +/- 0.1168 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 664 N_k = [500 164] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.01729745] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.38576083] relative max_delta = 2.658925e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4094 relative max_delta = 1.675920e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6238 relative max_delta = 1.320364e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6322 relative max_delta = 5.185247e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6323 relative max_delta = 7.999807e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6323 relative max_delta = 1.902673e-11 Converged to tolerance of 1.902673e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6323 Final dimensionless free energies f_k = [ 0. -1.63225553] Computing normalized weights... Interval 7, DeltaF=-1.6323 +/- 0.2750, Sum=8.6162 +/- 0.1251 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 500 N_k = [164 336] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.78644625] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.18326909] relative max_delta = 1.817563e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.2000 relative max_delta = 7.587605e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3496 relative max_delta = 6.368493e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3472 relative max_delta = 1.011295e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3472 relative max_delta = 2.399828e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3472 relative max_delta = 1.362225e-14 Converged to tolerance of 1.362225e-14 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3472 Final dimensionless free energies f_k = [ 0. -2.34722105] Computing normalized weights... Interval 8, DeltaF=-2.3472 +/- 0.2504, Sum=7.2259 +/- 0.1305 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 553 N_k = [336 217] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.25464699] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.77928539] relative max_delta = 1.887674e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7950 relative max_delta = 5.628786e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9368 relative max_delta = 4.827444e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9377 relative max_delta = 3.133908e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9377 relative max_delta = 1.676288e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9377 relative max_delta = 1.511685e-16 Converged to tolerance of 1.511685e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9377 Final dimensionless free energies f_k = [ 0. -2.93771054] Computing normalized weights... Interval 9, DeltaF=-2.9377 +/- 0.2152, Sum=5.4858 +/- 0.1334 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 597 N_k = [217 380] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.00158409] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06405637] relative max_delta = 5.871144e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0645 relative max_delta = 4.509418e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0689 relative max_delta = 4.041572e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0689 relative max_delta = 2.127364e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0689 relative max_delta = 5.847904e-13 Converged to tolerance of 5.847904e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0689 Final dimensionless free energies f_k = [ 0. -1.068854] Computing normalized weights... Interval 10, DeltaF=-1.0689 +/- 0.1538, Sum=4.8526 +/- 0.1341 Pairwise MBAR free energy: 4.8526 +/- 0.1341 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4062 N_k = [478 315 500 500 331 341 500 164 336 217 380] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.91216806 1.89743246 1.8699172 1.44396025 1.62915088 1.61487103 1.50438365 1.36579494 0.76043544 0.38259234] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.82047601 3.16103843 3.39244874 2.73863869 2.96981957 2.91396312 2.68782962 2.33926903 1.24625535 0.67471901] relative max_delta = 4.488002e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.1057 3.5872 4.2777 4.2806 4.6207 4.5150 4.1852 3.6815 2.3731 1.7463 relative max_delta = 3.572739e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8399 7.6294 11.9754 17.3486 18.6440 18.0921 16.7914 14.7981 11.5871 10.4843 relative max_delta = 7.521630e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.9215 9.0761 12.2686 16.2874 17.4766 16.9221 15.2758 12.9496 10.0106 8.9559 relative max_delta = 1.057718e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.9417 8.9772 12.2278 15.6275 16.8216 16.2639 14.6012 12.2519 9.3296 8.2731 relative max_delta = 4.147622e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.9403 8.9772 12.2175 15.5478 16.7440 16.1863 14.5236 12.1742 9.2519 8.1954 relative max_delta = 4.761350e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.9403 8.9772 12.2174 15.5468 16.7431 16.1853 14.5226 12.1732 9.2510 8.1945 relative max_delta = 6.032051e-05 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.9403 8.9772 12.2174 15.5468 16.7431 16.1853 14.5226 12.1732 9.2510 8.1945 relative max_delta = 1.008447e-08 Newton-Raphson iteration 7 current f_k for states with samples = 0.0000 6.9403 8.9772 12.2174 15.5468 16.7431 16.1853 14.5226 12.1732 9.2510 8.1945 relative max_delta = 3.607235e-15 Converged to tolerance of 3.607235e-15 in 8 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.9403 8.9772 12.2174 15.5468 16.7431 16.1853 14.5226 12.1732 9.2510 8.1945 Final dimensionless free energies f_k = [ 0. 6.94028681 8.97719483 12.21741363 15.54675632 16.743054 16.18531939 14.5226276 12.1732204 9.25095995 8.19445794] Computing normalized weights... DeltaMij: [[ 0. 4.11099106 5.31752775 7.23683035 9.20892436 9.91753615 9.58716911 8.60229467 7.21065305 5.47968906 4.85388346] [-4.11099106 0. 1.20653669 3.12583929 5.0979333 5.80654509 5.47617805 4.49130361 3.09966199 1.36869799 0.7428924 ] [-5.31752775 -1.20653669 0. 1.9193026 3.89139661 4.6000084 4.26964136 3.28476692 1.8931253 0.1621613 -0.46364429] [-7.23683035 -3.12583929 -1.9193026 0. 1.97209401 2.6807058 2.35033876 1.36546432 -0.0261773 -1.75714129 -2.38294689] [-9.20892436 -5.0979333 -3.89139661 -1.97209401 0. 0.70861179 0.37824475 -0.60662969 -1.99827131 -3.7292353 -4.3550409 ] [-9.91753615 -5.80654509 -4.6000084 -2.6807058 -0.70861179 0. -0.33036704 -1.31524148 -2.7068831 -4.4378471 -5.06365269] [-9.58716911 -5.47617805 -4.26964136 -2.35033876 -0.37824475 0.33036704 0. -0.98487444 -2.37651606 -4.10748006 -4.73328565] [-8.60229467 -4.49130361 -3.28476692 -1.36546432 0.60662969 1.31524148 0.98487444 0. -1.39164162 -3.12260562 -3.74841121] [-7.21065305 -3.09966199 -1.8931253 0.0261773 1.99827131 2.7068831 2.37651606 1.39164162 0. -1.73096399 -2.35676959] [-5.47968906 -1.36869799 -0.1621613 1.75714129 3.7292353 4.4378471 4.10748006 3.12260562 1.73096399 0. -0.6258056 ] [-4.85388346 -0.7428924 0.46364429 2.38294689 4.3550409 5.06365269 4.73328565 3.74841121 2.35676959 0.6258056 0. ]] dDeltaMij: [[ 0. 0.05488529 0.06951256 0.08160279 0.10133732 0.12598648 0.13442845 0.14404277 0.15424622 0.15973702 0.16178652] [ 0.05488529 0. 0.02428799 0.04804924 0.07697361 0.10737023 0.11716134 0.12807846 0.1394549 0.14550494 0.14775199] [ 0.06951256 0.02428799 0. 0.03345768 0.0690798 0.10186093 0.11213411 0.12349644 0.13525882 0.1414884 0.14379823] [ 0.08160279 0.04804924 0.03345768 0. 0.05407471 0.09230221 0.10352913 0.1157393 0.1282153 0.13477084 0.13719382] [ 0.10133732 0.07697361 0.0690798 0.05407471 0. 0.06227208 0.07788354 0.09350738 0.10856864 0.11623755 0.11903837] [ 0.12598648 0.10737023 0.10186093 0.09230221 0.06227208 0. 0.03113799 0.05999884 0.08154859 0.09150859 0.09504083] [ 0.13442845 0.11716134 0.11213411 0.10352913 0.07788354 0.03113799 0. 0.040703 0.06807008 0.07976147 0.08379111] [ 0.14404277 0.12807846 0.12349644 0.1157393 0.09350738 0.05999884 0.040703 0. 0.03498838 0.05232248 0.05835985] [ 0.15424622 0.1394549 0.13525882 0.1282153 0.10856864 0.08154859 0.06807008 0.03498838 0. 0.02288151 0.03257193] [ 0.15973702 0.14550494 0.1414884 0.13477084 0.11623755 0.09150859 0.07976147 0.05232248 0.02288151 0. 0.0122259 ] [ 0.16178652 0.14775199 0.14379823 0.13719382 0.11903837 0.09504083 0.08379111 0.05835985 0.03257193 0.0122259 0. ]] Replica 38 / 40 Computing statistical inefficiencies: lambda 0: g = 1.226 lambda 1: g = 1.655 lambda 2: g = 2.098 lambda 3: g = 3.297 lambda 4: g = 1.302 lambda 5: g = 1.704 lambda 6: g = 1.539 lambda 7: g = 1.287 lambda 8: g = 1.877 lambda 9: g = 1.712 lambda 10: g = 2.115 Subsampling data to produce uncorrelated samples... number of samples per lambda: [475 233 500 421 325 337 266 199 392 396 500] Method: EXP Forward EXP: Interval 1, DeltaF=6.9921 +/- 0.4594, Sum=4.1417 +/- 0.1250 Interval 2, DeltaF=1.9785 +/- 0.3290, Sum=5.3136 +/- 0.1405 Interval 3, DeltaF=3.0611 +/- 0.6893, Sum=7.1268 +/- 0.3146 Interval 4, DeltaF=4.2344 +/- 0.3737, Sum=9.6350 +/- 0.3253 Interval 5, DeltaF=1.1484 +/- 0.7208, Sum=10.3153 +/- 0.4478 Interval 6, DeltaF=-0.4980 +/- 0.3514, Sum=10.0203 +/- 0.4537 Interval 7, DeltaF=-1.8156 +/- 0.4485, Sum=8.9448 +/- 0.4691 Interval 8, DeltaF=-2.4758 +/- 0.3659, Sum=7.4783 +/- 0.4758 Interval 9, DeltaF=-2.8660 +/- 0.2470, Sum=5.7807 +/- 0.4771 Interval 10, DeltaF=-1.1144 +/- 0.1724, Sum=5.1206 +/- 0.4774 Forward EXP free energy: 5.1206 +/- 0.4774 Reverse EXP: Interval 1, DeltaF=7.0552 +/- 0.6410, Sum=4.1790 +/- 0.2434 Interval 2, DeltaF=2.0170 +/- 0.2785, Sum=5.3738 +/- 0.2477 Interval 3, DeltaF=3.3190 +/- 0.3749, Sum=7.3398 +/- 0.2613 Interval 4, DeltaF=3.3279 +/- 0.4913, Sum=9.3110 +/- 0.2979 Interval 5, DeltaF=0.7720 +/- 0.4723, Sum=9.7683 +/- 0.3259 Interval 6, DeltaF=-0.4562 +/- 0.3205, Sum=9.4981 +/- 0.3315 Interval 7, DeltaF=-1.6757 +/- 0.3755, Sum=8.5055 +/- 0.3419 Interval 8, DeltaF=-2.2906 +/- 0.3105, Sum=7.1487 +/- 0.3466 Interval 9, DeltaF=-3.0338 +/- 0.2783, Sum=5.3517 +/- 0.3496 Interval 10, DeltaF=-0.9882 +/- 0.1768, Sum=4.7663 +/- 0.3501 Reverse EXP free energy: 4.7663 +/- 0.3501 Averge of forward and reverse EXP: Interval 1, DeltaF=7.0236 +/- 0.2514, Sum=4.1604 +/- 0.0374 Interval 2, DeltaF=1.9978 +/- 0.0725, Sum=5.3437 +/- 0.0376 Interval 3, DeltaF=3.1901 +/- 0.2697, Sum=7.2333 +/- 0.0572 Interval 4, DeltaF=3.7812 +/- 0.1518, Sum=9.4730 +/- 0.0588 Interval 5, DeltaF=0.9602 +/- 0.3077, Sum=10.0418 +/- 0.0812 Interval 6, DeltaF=-0.4771 +/- 0.0874, Sum=9.7592 +/- 0.0813 Interval 7, DeltaF=-1.7457 +/- 0.1337, Sum=8.7252 +/- 0.0820 Interval 8, DeltaF=-2.3832 +/- 0.0898, Sum=7.3135 +/- 0.0822 Interval 9, DeltaF=-2.9499 +/- 0.0537, Sum=5.5662 +/- 0.0822 Interval 10, DeltaF=-1.0513 +/- 0.0235, Sum=4.9435 +/- 0.0822 Average EXP free energy: 4.9435 +/- 0.0822 Interval 1, DeltaF=7.0552 +/- 0.3162, Sum=4.1790 +/- 0.0592 Interval 2, DeltaF=1.9785 +/- 0.2444, Sum=5.3510 +/- 0.0690 Interval 3, DeltaF=3.3190 +/- 0.4678, Sum=7.3169 +/- 0.1469 Interval 4, DeltaF=4.2344 +/- 0.5880, Sum=9.8251 +/- 0.2520 Interval 5, DeltaF=0.7720 +/- 0.5736, Sum=10.2824 +/- 0.3186 Interval 6, DeltaF=-0.4980 +/- 0.8283, Sum=9.9875 +/- 0.5164 Interval 7, DeltaF=-1.6757 +/- 0.6187, Sum=8.9949 +/- 0.5640 Interval 8, DeltaF=-2.4758 +/- 0.8681, Sum=7.5284 +/- 0.7192 Interval 9, DeltaF=-3.0338 +/- 0.6397, Sum=5.7314 +/- 0.7590 Interval 10, DeltaF=-1.1144 +/- 0.8770, Sum=5.0713 +/- 0.8852 Double-Wide EXP free energy: 5.0713 +/- 0.8852 Method: BAR Interval 1, DeltaF=6.8978 +/- 0.3228, Sum=4.0858 +/- 0.0617 Interval 2, DeltaF=2.0080 +/- 0.2138, Sum=5.2752 +/- 0.0674 Interval 3, DeltaF=3.3261 +/- 0.2502, Sum=7.2454 +/- 0.0769 Interval 4, DeltaF=3.3134 +/- 0.3121, Sum=9.2081 +/- 0.0962 Interval 5, DeltaF=1.0479 +/- 0.3523, Sum=9.8288 +/- 0.1210 Interval 6, DeltaF=-0.5558 +/- 0.2505, Sum=9.4996 +/- 0.1266 Interval 7, DeltaF=-1.6454 +/- 0.2933, Sum=8.5250 +/- 0.1365 Interval 8, DeltaF=-2.2706 +/- 0.2394, Sum=7.1800 +/- 0.1407 Interval 9, DeltaF=-2.9288 +/- 0.2050, Sum=5.4452 +/- 0.1428 Interval 10, DeltaF=-1.0564 +/- 0.1410, Sum=4.8194 +/- 0.1433 BAR free energy: 4.8194 +/- 0.1433 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.9720 +/- 0.6421, Sum=4.1298 +/- 0.2442 Interval 2, DeltaF=2.0201 +/- 0.2020, Sum=5.3264 +/- 0.2454 Interval 3, DeltaF=3.3939 +/- 0.3445, Sum=7.3367 +/- 0.2552 Interval 4, DeltaF=3.6069 +/- 0.3952, Sum=9.4732 +/- 0.2715 Interval 5, DeltaF=1.1056 +/- 0.3763, Sum=10.1281 +/- 0.2842 Interval 6, DeltaF=-0.5448 +/- 0.2383, Sum=9.8053 +/- 0.2861 Interval 7, DeltaF=-1.6289 +/- 0.2767, Sum=8.8405 +/- 0.2897 Interval 8, DeltaF=-2.2806 +/- 0.3711, Sum=7.4896 +/- 0.3010 Interval 9, DeltaF=-2.9910 +/- 0.3336, Sum=5.7180 +/- 0.3081 Interval 10, DeltaF=-1.0266 +/- 0.2175, Sum=5.1099 +/- 0.3094 Unopt. BAR free energy: 5.1099 +/- 0.3094 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.8965 +/- 0.3215, Sum=4.0851 +/- 0.0612 Interval 2, DeltaF=2.0081 +/- 0.2134, Sum=5.2745 +/- 0.0669 Interval 3, DeltaF=3.3345 +/- 0.2549, Sum=7.2497 +/- 0.0772 Interval 4, DeltaF=3.3280 +/- 0.3220, Sum=9.2210 +/- 0.0986 Interval 5, DeltaF=1.0506 +/- 0.3536, Sum=9.8433 +/- 0.1233 Interval 6, DeltaF=-0.5643 +/- 0.2650, Sum=9.5091 +/- 0.1302 Interval 7, DeltaF=-1.6567 +/- 0.3031, Sum=8.5278 +/- 0.1411 Interval 8, DeltaF=-2.2674 +/- 0.2496, Sum=7.1847 +/- 0.1458 Interval 9, DeltaF=-2.9276 +/- 0.2044, Sum=5.4506 +/- 0.1479 Interval 10, DeltaF=-1.0548 +/- 0.1439, Sum=4.8258 +/- 0.1484 Postopt. BAR free energy: 4.8258 +/- 0.1484 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 708 N_k = [475 233] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.88157111] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 5.17834854] relative max_delta = 2.504230e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.3664 relative max_delta = 3.504248e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 7.0192 relative max_delta = 2.354654e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8985 relative max_delta = 1.749666e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.8978 relative max_delta = 1.011827e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.8978 relative max_delta = 3.338932e-09 Converged to tolerance of 3.338932e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.8978 Final dimensionless free energies f_k = [ 0. 6.89777437] Computing normalized weights... Interval 1, DeltaF=6.8978 +/- 0.3228, Sum=4.0858 +/- 0.0617 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 733 N_k = [233 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.53147085] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.8890463] relative max_delta = 1.892889e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9008 relative max_delta = 6.167238e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 2.0066 relative max_delta = 5.273573e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 2.0080 relative max_delta = 7.124888e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 2.0080 relative max_delta = 1.357004e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 2.0080 relative max_delta = 3.538527e-15 Converged to tolerance of 3.538527e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 2.0080 Final dimensionless free energies f_k = [ 0. 2.00801863] Computing normalized weights... Interval 2, DeltaF=2.0080 +/- 0.2138, Sum=5.2752 +/- 0.0674 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 921 N_k = [500 421] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.68175213] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.52394275] relative max_delta = 3.336806e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.6092 relative max_delta = 3.266791e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.3644 relative max_delta = 2.244720e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3262 relative max_delta = 1.148060e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3261 relative max_delta = 1.910756e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3261 relative max_delta = 5.463522e-11 Converged to tolerance of 5.463522e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3261 Final dimensionless free energies f_k = [ 0. 3.32614025] Computing normalized weights... Interval 3, DeltaF=3.3261 +/- 0.2502, Sum=7.2454 +/- 0.0769 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 746 N_k = [421 325] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.96298921] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.67499812] relative max_delta = 4.250804e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8740 relative max_delta = 1.061829e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.5885 relative max_delta = 4.777740e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3229 relative max_delta = 7.991990e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3135 relative max_delta = 2.844820e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3134 relative max_delta = 3.477228e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3134 relative max_delta = 5.188960e-12 Converged to tolerance of 5.188960e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3134 Final dimensionless free energies f_k = [ 0. 3.31344982] Computing normalized weights... Interval 4, DeltaF=3.3134 +/- 0.3121, Sum=9.2081 +/- 0.0962 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 662 N_k = [325 337] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.26757604] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.47123415] relative max_delta = 4.321803e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.5323 relative max_delta = 1.147263e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.0753 relative max_delta = 5.049908e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.0480 relative max_delta = 2.606716e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.0479 relative max_delta = 7.756040e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.0479 relative max_delta = 6.816292e-10 Converged to tolerance of 6.816292e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.0479 Final dimensionless free energies f_k = [ 0. 1.04794015] Computing normalized weights... Interval 5, DeltaF=1.0479 +/- 0.3523, Sum=9.8288 +/- 0.1210 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 603 N_k = [337 266] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.36083485] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.48502697] relative max_delta = 2.560520e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4921 relative max_delta = 1.430429e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5555 relative max_delta = 1.141757e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 5.977950e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 1.693463e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5558 relative max_delta = 9.987232e-16 Converged to tolerance of 9.987232e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5558 Final dimensionless free energies f_k = [ 0. -0.55582121] Computing normalized weights... Interval 6, DeltaF=-0.5558 +/- 0.2505, Sum=9.4996 +/- 0.1266 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 465 N_k = [266 199] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97947278] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.35279284] relative max_delta = 2.759625e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3814 relative max_delta = 2.073262e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6403 relative max_delta = 1.578096e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6454 relative max_delta = 3.102057e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6454 relative max_delta = 1.289833e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6454 relative max_delta = 2.219916e-13 Converged to tolerance of 2.219916e-13 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6454 Final dimensionless free energies f_k = [ 0. -1.64539279] Computing normalized weights... Interval 7, DeltaF=-1.6454 +/- 0.2933, Sum=8.5250 +/- 0.1365 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 591 N_k = [199 392] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.73367412] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.11466419] relative max_delta = 1.801658e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1305 relative max_delta = 7.431665e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.2725 relative max_delta = 6.249623e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.2706 relative max_delta = 8.249512e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.2706 relative max_delta = 1.324089e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.2706 relative max_delta = 3.324829e-15 Converged to tolerance of 3.324829e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.2706 Final dimensionless free energies f_k = [ 0. -2.27064788] Computing normalized weights... Interval 8, DeltaF=-2.2706 +/- 0.2394, Sum=7.1800 +/- 0.1407 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 788 N_k = [392 396] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.19575773] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.73273567] relative max_delta = 1.964983e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7525 relative max_delta = 7.179209e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9300 relative max_delta = 6.058182e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9288 relative max_delta = 4.105217e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9288 relative max_delta = 1.240383e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9288 relative max_delta = 1.819541e-15 Converged to tolerance of 1.819541e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9288 Final dimensionless free energies f_k = [ 0. -2.92879887] Computing normalized weights... Interval 9, DeltaF=-2.9288 +/- 0.2050, Sum=5.4452 +/- 0.1428 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 896 N_k = [396 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.97592479] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.0499304] relative max_delta = 7.048620e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0506 relative max_delta = 6.160448e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0564 relative max_delta = 5.513422e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0564 relative max_delta = 1.743549e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0564 relative max_delta = 1.731964e-13 Converged to tolerance of 1.731964e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0564 Final dimensionless free energies f_k = [ 0. -1.05640015] Computing normalized weights... Interval 10, DeltaF=-1.0564 +/- 0.1410, Sum=4.8194 +/- 0.1433 Pairwise MBAR free energy: 4.8194 +/- 0.1433 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4044 N_k = [475 233 500 421 325 337 266 199 392 396 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.89540718 1.88173481 1.75024557 1.46856288 1.56428757 1.6545948 1.72913936 1.64538264 0.85500327 0.36158212] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.75912828 3.10791988 3.19158452 2.77408079 2.93442698 3.03370898 3.04265961 2.7195205 1.38536952 0.6985459 ] relative max_delta = 4.516061e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.0181 3.5012 4.0813 4.2085 4.4799 4.5246 4.4146 3.9068 2.3842 1.6568 relative max_delta = 3.415735e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5182 7.2404 11.7764 16.3537 17.5822 17.1211 15.8720 13.6463 10.4916 9.4092 relative max_delta = 7.452025e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.8900 8.9521 12.1962 15.8479 16.9477 16.3997 14.7468 12.4678 9.5791 8.5173 relative max_delta = 1.009976e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.9117 8.8970 12.1993 15.5003 16.5989 16.0442 14.3783 12.0971 9.2171 8.1562 relative max_delta = 2.233385e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.9110 8.8969 12.1960 15.4804 16.5796 16.0250 14.3590 12.0778 9.1978 8.1370 relative max_delta = 1.200387e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.9110 8.8969 12.1960 15.4803 16.5796 16.0249 14.3589 12.0778 9.1977 8.1369 relative max_delta = 3.103030e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.9110 8.8969 12.1960 15.4803 16.5796 16.0249 14.3589 12.0778 9.1977 8.1369 relative max_delta = 2.178996e-11 Converged to tolerance of 2.178996e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.9110 8.8969 12.1960 15.4803 16.5796 16.0249 14.3589 12.0778 9.1977 8.1369 Final dimensionless free energies f_k = [ 0. 6.91102229 8.89689248 12.19602891 15.48031647 16.57957738 16.02491044 14.35892966 12.07778813 9.19774397 8.13690441] Computing normalized weights... DeltaMij: [[ 0. 4.09365659 5.26996167 7.22416338 9.16956956 9.82070285 9.49215291 8.50533027 7.15412495 5.44816724 4.81979235] [-4.09365659 0. 1.17630508 3.13050679 5.07591296 5.72704625 5.39849631 4.41167368 3.06046836 1.35451065 0.72613576] [-5.26996167 -1.17630508 0. 1.95420171 3.89960789 4.55074117 4.22219123 3.2353686 1.88416328 0.17820557 -0.45016932] [-7.22416338 -3.13050679 -1.95420171 0. 1.94540617 2.59653946 2.26798952 1.28116689 -0.07003843 -1.77599614 -2.40437103] [-9.16956956 -5.07591296 -3.89960789 -1.94540617 0. 0.65113329 0.32258335 -0.66423928 -2.0154446 -3.72140231 -4.3497772 ] [-9.82070285 -5.72704625 -4.55074117 -2.59653946 -0.65113329 0. -0.32854994 -1.31537257 -2.66657789 -4.3725356 -5.00091049] [-9.49215291 -5.39849631 -4.22219123 -2.26798952 -0.32258335 0.32854994 0. -0.98682263 -2.33802795 -4.04398566 -4.67236055] [-8.50533027 -4.41167368 -3.2353686 -1.28116689 0.66423928 1.31537257 0.98682263 0. -1.35120532 -3.05716303 -3.68553792] [-7.15412495 -3.06046836 -1.88416328 0.07003843 2.0154446 2.66657789 2.33802795 1.35120532 0. -1.70595771 -2.3343326 ] [-5.44816724 -1.35451065 -0.17820557 1.77599614 3.72140231 4.3725356 4.04398566 3.05716303 1.70595771 0. -0.62837489] [-4.81979235 -0.72613576 0.45016932 2.40437103 4.3497772 5.00091049 4.67236055 3.68553792 2.3343326 0.62837489 0. ]] dDeltaMij: [[ 0. 0.05869054 0.07516752 0.08740455 0.1080861 0.13537579 0.14493067 0.15711763 0.16539428 0.16963606 0.17107584] [ 0.05869054 0. 0.02566121 0.05025531 0.08114717 0.11501802 0.12612468 0.13995886 0.14919049 0.15387959 0.15546535] [ 0.07516752 0.02566121 0. 0.03546241 0.07322738 0.10957427 0.12118089 0.13552069 0.14503509 0.14985427 0.15148218] [ 0.08740455 0.05025531 0.03546241 0. 0.05673946 0.09926302 0.1119446 0.12732883 0.13741161 0.14248886 0.14419995] [ 0.1080861 0.08114717 0.07322738 0.05673946 0. 0.06996521 0.08697787 0.10605152 0.11796692 0.12384394 0.12580886] [ 0.13537579 0.11501802 0.10957427 0.09926302 0.06996521 0. 0.03569454 0.06986798 0.08693096 0.0947513 0.09730535] [ 0.14493067 0.12612468 0.12118089 0.1119446 0.08697787 0.03569454 0. 0.04568359 0.06816119 0.0779371 0.08102412] [ 0.15711763 0.13995886 0.13552069 0.12732883 0.10605152 0.06986798 0.04568359 0. 0.03087641 0.04698902 0.05201747] [ 0.16539428 0.14919049 0.14503509 0.13741161 0.11796692 0.08693096 0.06816119 0.03087641 0. 0.02092975 0.02891833] [ 0.16963606 0.15387959 0.14985427 0.14248886 0.12384394 0.0947513 0.0779371 0.04698902 0.02092975 0. 0.01031947] [ 0.17107584 0.15546535 0.15148218 0.14419995 0.12580886 0.09730535 0.08102412 0.05201747 0.02891833 0.01031947 0. ]] Replica 39 / 40 Computing statistical inefficiencies: lambda 0: g = 1.601 lambda 1: g = 1.617 lambda 2: g = 3.564 lambda 3: g = 1.522 lambda 4: g = 2.161 lambda 5: g = 1.045 lambda 6: g = 1.626 lambda 7: g = 1.554 lambda 8: g = 2.180 lambda 9: g = 1.407 lambda 10: g = 1.699 Subsampling data to produce uncorrelated samples... number of samples per lambda: [333 407 472 500 269 500 261 292 178 485 322] Method: EXP Forward EXP: Interval 1, DeltaF=7.5210 +/- 0.4573, Sum=4.4549 +/- 0.1239 Interval 2, DeltaF=1.8488 +/- 0.2754, Sum=5.5501 +/- 0.1318 Interval 3, DeltaF=3.1144 +/- 0.4684, Sum=7.3948 +/- 0.1851 Interval 4, DeltaF=3.9639 +/- 0.4857, Sum=9.7428 +/- 0.2319 Interval 5, DeltaF=2.3358 +/- 0.4337, Sum=11.1264 +/- 0.2573 Interval 6, DeltaF=-0.6320 +/- 0.5772, Sum=10.7520 +/- 0.3243 Interval 7, DeltaF=-1.5271 +/- 0.4097, Sum=9.8474 +/- 0.3391 Interval 8, DeltaF=-2.0789 +/- 0.3011, Sum=8.6160 +/- 0.3434 Interval 9, DeltaF=-3.0698 +/- 0.3216, Sum=6.7977 +/- 0.3488 Interval 10, DeltaF=-1.0628 +/- 0.1630, Sum=6.1681 +/- 0.3492 Forward EXP free energy: 6.1681 +/- 0.3492 Reverse EXP: Interval 1, DeltaF=6.0172 +/- 0.4558, Sum=3.5642 +/- 0.1231 Interval 2, DeltaF=2.0576 +/- 0.3123, Sum=4.7830 +/- 0.1360 Interval 3, DeltaF=3.1673 +/- 0.3873, Sum=6.6591 +/- 0.1624 Interval 4, DeltaF=3.4069 +/- 0.4123, Sum=8.6772 +/- 0.1911 Interval 5, DeltaF=1.1935 +/- 0.4221, Sum=9.3841 +/- 0.2183 Interval 6, DeltaF=-0.5284 +/- 0.3200, Sum=9.0711 +/- 0.2266 Interval 7, DeltaF=-1.5320 +/- 0.3489, Sum=8.1636 +/- 0.2378 Interval 8, DeltaF=-2.6335 +/- 0.3317, Sum=6.6037 +/- 0.2466 Interval 9, DeltaF=-2.9381 +/- 0.2706, Sum=4.8634 +/- 0.2503 Interval 10, DeltaF=-1.0753 +/- 0.2052, Sum=4.2264 +/- 0.2516 Reverse EXP free energy: 4.2264 +/- 0.2516 Averge of forward and reverse EXP: Interval 1, DeltaF=6.7691 +/- 0.1604, Sum=4.0096 +/- 0.0152 Interval 2, DeltaF=1.9532 +/- 0.0672, Sum=5.1666 +/- 0.0155 Interval 3, DeltaF=3.1408 +/- 0.1446, Sum=7.0270 +/- 0.0198 Interval 4, DeltaF=3.6854 +/- 0.1583, Sum=9.2100 +/- 0.0248 Interval 5, DeltaF=1.7646 +/- 0.1410, Sum=10.2552 +/- 0.0274 Interval 6, DeltaF=-0.5802 +/- 0.1897, Sum=9.9115 +/- 0.0347 Interval 7, DeltaF=-1.5296 +/- 0.1128, Sum=9.0055 +/- 0.0355 Interval 8, DeltaF=-2.3562 +/- 0.0776, Sum=7.6099 +/- 0.0357 Interval 9, DeltaF=-3.0039 +/- 0.0690, Sum=5.8305 +/- 0.0358 Interval 10, DeltaF=-1.0691 +/- 0.0271, Sum=5.1973 +/- 0.0358 Average EXP free energy: 5.1973 +/- 0.0358 Interval 1, DeltaF=6.0172 +/- 0.1599, Sum=3.5642 +/- 0.0151 Interval 2, DeltaF=1.8488 +/- 0.2350, Sum=4.6594 +/- 0.0360 Interval 3, DeltaF=3.1673 +/- 0.2752, Sum=6.5355 +/- 0.0575 Interval 4, DeltaF=3.9639 +/- 0.3855, Sum=8.8834 +/- 0.1052 Interval 5, DeltaF=1.1935 +/- 0.3770, Sum=9.5904 +/- 0.1347 Interval 6, DeltaF=-0.6320 +/- 0.5378, Sum=9.2160 +/- 0.2180 Interval 7, DeltaF=-1.5320 +/- 0.4268, Sum=8.3085 +/- 0.2432 Interval 8, DeltaF=-2.0789 +/- 0.6271, Sum=7.0771 +/- 0.3368 Interval 9, DeltaF=-2.9381 +/- 0.4565, Sum=5.3368 +/- 0.3587 Interval 10, DeltaF=-1.0628 +/- 0.6413, Sum=4.7072 +/- 0.4336 Double-Wide EXP free energy: 4.7072 +/- 0.4336 Method: BAR Interval 1, DeltaF=6.7544 +/- 0.3201, Sum=4.0009 +/- 0.0607 Interval 2, DeltaF=1.9251 +/- 0.1965, Sum=5.1412 +/- 0.0649 Interval 3, DeltaF=3.1885 +/- 0.2475, Sum=7.0299 +/- 0.0743 Interval 4, DeltaF=3.4379 +/- 0.3083, Sum=9.0662 +/- 0.0932 Interval 5, DeltaF=1.2008 +/- 0.3238, Sum=9.7775 +/- 0.1120 Interval 6, DeltaF=-0.5119 +/- 0.2412, Sum=9.4743 +/- 0.1172 Interval 7, DeltaF=-1.5756 +/- 0.2711, Sum=8.5410 +/- 0.1250 Interval 8, DeltaF=-2.3081 +/- 0.2567, Sum=7.1739 +/- 0.1310 Interval 9, DeltaF=-2.9697 +/- 0.2120, Sum=5.4148 +/- 0.1337 Interval 10, DeltaF=-1.0726 +/- 0.1420, Sum=4.7795 +/- 0.1342 BAR free energy: 4.7795 +/- 0.1342 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=7.4598 +/- 0.4578, Sum=4.4187 +/- 0.1242 Interval 2, DeltaF=1.8924 +/- 0.2507, Sum=5.5397 +/- 0.1296 Interval 3, DeltaF=3.1798 +/- 0.3146, Sum=7.4232 +/- 0.1423 Interval 4, DeltaF=3.4798 +/- 0.4491, Sum=9.4844 +/- 0.1858 Interval 5, DeltaF=1.2422 +/- 0.3446, Sum=10.2202 +/- 0.1986 Interval 6, DeltaF=-0.5180 +/- 0.2196, Sum=9.9134 +/- 0.2007 Interval 7, DeltaF=-1.5547 +/- 0.2857, Sum=8.9925 +/- 0.2064 Interval 8, DeltaF=-2.4754 +/- 0.2819, Sum=7.5262 +/- 0.2117 Interval 9, DeltaF=-2.9415 +/- 0.4750, Sum=5.7838 +/- 0.2504 Interval 10, DeltaF=-1.0788 +/- 0.1618, Sum=5.1448 +/- 0.2508 Unopt. BAR free energy: 5.1448 +/- 0.2508 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.7207 +/- 0.3215, Sum=3.9809 +/- 0.0612 Interval 2, DeltaF=1.9260 +/- 0.1976, Sum=5.1218 +/- 0.0655 Interval 3, DeltaF=3.1922 +/- 0.2489, Sum=7.0127 +/- 0.0750 Interval 4, DeltaF=3.4487 +/- 0.3285, Sum=9.0555 +/- 0.0986 Interval 5, DeltaF=1.2052 +/- 0.3270, Sum=9.7693 +/- 0.1172 Interval 6, DeltaF=-0.5050 +/- 0.2645, Sum=9.4702 +/- 0.1243 Interval 7, DeltaF=-1.5822 +/- 0.2764, Sum=8.5331 +/- 0.1323 Interval 8, DeltaF=-2.3299 +/- 0.2495, Sum=7.1530 +/- 0.1373 Interval 9, DeltaF=-2.9701 +/- 0.2093, Sum=5.3937 +/- 0.1398 Interval 10, DeltaF=-1.0730 +/- 0.1364, Sum=4.7581 +/- 0.1402 Postopt. BAR free energy: 4.7581 +/- 0.1402 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 740 N_k = [333 407] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.42894846] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.74825295] relative max_delta = 2.778505e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 4.9388 relative max_delta = 3.857925e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.6644 relative max_delta = 2.589272e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7542 relative max_delta = 1.330465e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7544 relative max_delta = 2.996945e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7544 relative max_delta = 1.470684e-10 Converged to tolerance of 1.470684e-10 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7544 Final dimensionless free energies f_k = [ 0. 6.75444082] Computing normalized weights... Interval 1, DeltaF=6.7544 +/- 0.3201, Sum=4.0009 +/- 0.0607 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 879 N_k = [407 472] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.49647934] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.82074456] relative max_delta = 1.780948e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8311 relative max_delta = 5.682169e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9248 relative max_delta = 4.867212e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9251 relative max_delta = 1.133492e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9251 relative max_delta = 8.028487e-10 Converged to tolerance of 8.028487e-10 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9251 Final dimensionless free energies f_k = [ 0. 1.92505348] Computing normalized weights... Interval 2, DeltaF=1.9251 +/- 0.1965, Sum=5.1412 +/- 0.0649 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 972 N_k = [472 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.59405737] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.39679552] relative max_delta = 3.349214e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.4793 relative max_delta = 3.328185e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2140 relative max_delta = 2.285821e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.1885 relative max_delta = 7.980590e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.1885 relative max_delta = 4.841231e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.1885 relative max_delta = 1.854489e-12 Converged to tolerance of 1.854489e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.1885 Final dimensionless free energies f_k = [ 0. 3.1885051] Computing normalized weights... Interval 3, DeltaF=3.1885 +/- 0.2475, Sum=7.0299 +/- 0.0743 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 769 N_k = [500 269] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.92178999] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.65389561] relative max_delta = 4.426553e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.9059 relative max_delta = 1.322115e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.9730 relative max_delta = 5.202905e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.4828 relative max_delta = 1.407449e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.4382 relative max_delta = 1.296418e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.4379 relative max_delta = 1.051711e-04 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.4379 relative max_delta = 6.883633e-09 Converged to tolerance of 6.883633e-09 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.4379 Final dimensionless free energies f_k = [ 0. 3.43785531] Computing normalized weights... Interval 4, DeltaF=3.4379 +/- 0.3083, Sum=9.0662 +/- 0.0932 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 769 N_k = [269 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.36187259] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.6239043] relative max_delta = 4.199870e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.6840 relative max_delta = 8.787470e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.2200 relative max_delta = 4.393435e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.2009 relative max_delta = 1.595521e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.2008 relative max_delta = 1.933019e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.2008 relative max_delta = 2.847700e-11 Converged to tolerance of 2.847700e-11 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.2008 Final dimensionless free energies f_k = [ 0. 1.20083589] Computing normalized weights... Interval 5, DeltaF=1.2008 +/- 0.3238, Sum=9.7775 +/- 0.1120 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 761 N_k = [500 261] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.33091717] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.44629395] relative max_delta = 2.585220e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4528 relative max_delta = 1.436024e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5114 relative max_delta = 1.146375e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5119 relative max_delta = 9.242356e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5119 relative max_delta = 6.082151e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5119 relative max_delta = 7.157163e-15 Converged to tolerance of 7.157163e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5119 Final dimensionless free energies f_k = [ 0. -0.51189781] Computing normalized weights... Interval 6, DeltaF=-0.5119 +/- 0.2412, Sum=9.4743 +/- 0.1172 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 553 N_k = [261 292] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98845761] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.33508936] relative max_delta = 2.596319e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.3590 relative max_delta = 1.761719e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.5747 relative max_delta = 1.369430e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.5756 relative max_delta = 5.901539e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.5756 relative max_delta = 1.561737e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.5756 relative max_delta = 2.254830e-15 Converged to tolerance of 2.254830e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.5756 Final dimensionless free energies f_k = [ 0. -1.57560186] Computing normalized weights... Interval 7, DeltaF=-1.5756 +/- 0.2711, Sum=8.5410 +/- 0.1250 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 470 N_k = [292 178] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.59667729] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.07566054] relative max_delta = 2.307618e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.0986 relative max_delta = 1.092988e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3056 relative max_delta = 8.976446e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3081 relative max_delta = 1.100971e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3081 relative max_delta = 1.937064e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3081 relative max_delta = 4.617719e-15 Converged to tolerance of 4.617719e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3081 Final dimensionless free energies f_k = [ 0. -2.30809642] Computing normalized weights... Interval 8, DeltaF=-2.3081 +/- 0.2567, Sum=7.1739 +/- 0.1310 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 663 N_k = [178 485] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.52142753] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.87820247] relative max_delta = 1.239576e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.8875 relative max_delta = 3.220156e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.9709 relative max_delta = 2.806672e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.9697 relative max_delta = 4.131895e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.9697 relative max_delta = 8.828665e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.9697 relative max_delta = 5.233980e-15 Converged to tolerance of 5.233980e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.9697 Final dimensionless free energies f_k = [ 0. -2.96965634] Computing normalized weights... Interval 9, DeltaF=-2.9697 +/- 0.2120, Sum=5.4148 +/- 0.1337 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 807 N_k = [485 322] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.98791268] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.06630845] relative max_delta = 7.352072e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0669 relative max_delta = 5.851904e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 5.239687e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 2.439429e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0726 relative max_delta = 5.335007e-13 Converged to tolerance of 5.335007e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0726 Final dimensionless free energies f_k = [ 0. -1.07255527] Computing normalized weights... Interval 10, DeltaF=-1.0726 +/- 0.1420, Sum=4.7795 +/- 0.1342 Pairwise MBAR free energy: 4.7795 +/- 0.1342 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4019 N_k = [333 407 472 500 269 500 261 292 178 485 322] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.03749233 2.0840777 2.16843082 1.67269806 1.7808736 1.84054335 1.88656513 1.8246866 1.13025406 0.60937091] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.0316257 3.49664863 3.88169862 3.11261134 3.25444656 3.31114933 3.27705895 3.00956304 1.84671584 1.15031564] relative max_delta = 4.413706e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.2693 3.8664 4.6621 4.6838 4.9434 4.9543 4.8048 4.3620 2.9960 2.2584 relative max_delta = 3.408985e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.5517 7.3488 11.4419 17.6592 18.9673 18.5545 17.2982 15.1892 12.0135 10.9113 relative max_delta = 7.393743e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.7439 8.7724 12.1015 16.4860 17.6811 17.1874 15.5861 13.3040 10.3624 9.2846 relative max_delta = 1.066196e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.7896 8.7255 11.9499 15.5418 16.7456 16.2448 14.6338 12.3359 9.4112 8.3331 relative max_delta = 5.781619e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.7881 8.7257 11.9323 15.3744 16.5841 16.0832 14.4723 12.1742 9.2496 8.1715 relative max_delta = 1.009464e-02 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.7881 8.7256 11.9319 15.3694 16.5793 16.0784 14.4675 12.1694 9.2448 8.1667 relative max_delta = 3.037988e-04 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.7881 8.7256 11.9319 15.3694 16.5793 16.0784 14.4675 12.1694 9.2448 8.1667 relative max_delta = 2.754534e-07 Newton-Raphson iteration 7 current f_k for states with samples = 0.0000 6.7881 8.7256 11.9319 15.3694 16.5793 16.0784 14.4675 12.1694 9.2448 8.1667 relative max_delta = 2.233937e-13 Converged to tolerance of 2.233937e-13 in 8 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.7881 8.7256 11.9319 15.3694 16.5793 16.0784 14.4675 12.1694 9.2448 8.1667 Final dimensionless free energies f_k = [ 0. 6.78813654 8.72562813 11.93193872 15.36937648 16.5792658 16.07842922 14.4674603 12.16938652 9.24476545 8.16670427] Computing normalized weights... DeltaMij: [[ 0. 4.02086678 5.1685154 7.0677329 9.10385566 9.82051828 9.52385407 8.56961702 7.2083821 5.47601982 4.83744392] [-4.02086678 0. 1.14764862 3.04686613 5.08298888 5.79965151 5.5029873 4.54875024 3.18751532 1.45515304 0.81657715] [-5.1685154 -1.14764862 0. 1.89921751 3.93534026 4.65200288 4.35533867 3.40110162 2.0398667 0.30750442 -0.33107147] [-7.0677329 -3.04686613 -1.89921751 0. 2.03612275 2.75278538 2.45612117 1.50188412 0.1406492 -1.59171308 -2.23028898] [-9.10385566 -5.08298888 -3.93534026 -2.03612275 0. 0.71666263 0.41999842 -0.53423864 -1.89547355 -3.62783584 -4.26641173] [-9.82051828 -5.79965151 -4.65200288 -2.75278538 -0.71666263 0. -0.29666421 -1.25090126 -2.61213618 -4.34449846 -4.98307436] [-9.52385407 -5.5029873 -4.35533867 -2.45612117 -0.41999842 0.29666421 0. -0.95423705 -2.31547197 -4.04783425 -4.68641015] [-8.56961702 -4.54875024 -3.40110162 -1.50188412 0.53423864 1.25090126 0.95423705 0. -1.36123492 -3.0935972 -3.7321731 ] [-7.2083821 -3.18751532 -2.0398667 -0.1406492 1.89547355 2.61213618 2.31547197 1.36123492 0. -1.73236228 -2.37093818] [-5.47601982 -1.45515304 -0.30750442 1.59171308 3.62783584 4.34449846 4.04783425 3.0935972 1.73236228 0. -0.6385759 ] [-4.83744392 -0.81657715 0.33107147 2.23028898 4.26641173 4.98307436 4.68641015 3.7321731 2.37093818 0.6385759 0. ]] dDeltaMij: [[ 0. 0.05912895 0.07148175 0.08283835 0.10240128 0.12711453 0.13495031 0.1464087 0.15549815 0.16124927 0.16314309] [ 0.05912895 0. 0.02212252 0.04636165 0.07599941 0.10699571 0.11619623 0.12932704 0.13953369 0.1459154 0.14800556] [ 0.07148175 0.02212252 0. 0.03361594 0.06922455 0.10229548 0.11188318 0.1254662 0.13596299 0.1425047 0.14464414] [ 0.08283835 0.04636165 0.03361594 0. 0.05419905 0.09272945 0.1032102 0.11779751 0.12892021 0.1358016 0.13804497] [ 0.10240128 0.07599941 0.06922455 0.05419905 0. 0.06072962 0.07571989 0.09464905 0.10817839 0.11629369 0.11890569] [ 0.12711453 0.10699571 0.10229548 0.09272945 0.06072962 0. 0.03214814 0.06479285 0.08333879 0.09363009 0.09685511] [ 0.13495031 0.11619623 0.11188318 0.1032102 0.07571989 0.03214814 0. 0.04263068 0.06693617 0.07946846 0.08324614] [ 0.1464087 0.12932704 0.1254662 0.11779751 0.09464905 0.06479285 0.04263068 0. 0.03401588 0.05290938 0.05844157] [ 0.15549815 0.13953369 0.13596299 0.12892021 0.10817839 0.08333879 0.06693617 0.03401588 0. 0.02365088 0.03221518] [ 0.16124927 0.1459154 0.1425047 0.1358016 0.11629369 0.09363009 0.07946846 0.05290938 0.02365088 0. 0.01107122] [ 0.16314309 0.14800556 0.14464414 0.13804497 0.11890569 0.09685511 0.08324614 0.05844157 0.03221518 0.01107122 0. ]] Replica 40 / 40 Computing statistical inefficiencies: lambda 0: g = 1.981 lambda 1: g = 1.497 lambda 2: g = 1.070 lambda 3: g = 2.171 lambda 4: g = 1.458 lambda 5: g = 1.363 lambda 6: g = 1.749 lambda 7: g = 1.273 lambda 8: g = 2.479 lambda 9: g = 1.308 lambda 10: g = 1.658 Subsampling data to produce uncorrelated samples... number of samples per lambda: [343 500 319 500 500 500 350 160 179 364 447] Method: EXP Forward EXP: Interval 1, DeltaF=6.5272 +/- 0.5454, Sum=3.8663 +/- 0.1762 Interval 2, DeltaF=1.9689 +/- 0.2593, Sum=5.0325 +/- 0.1806 Interval 3, DeltaF=3.4241 +/- 0.4058, Sum=7.0607 +/- 0.2053 Interval 4, DeltaF=3.7543 +/- 0.4738, Sum=9.2845 +/- 0.2446 Interval 5, DeltaF=2.0036 +/- 0.4791, Sum=10.4713 +/- 0.2798 Interval 6, DeltaF=-0.6128 +/- 0.5638, Sum=10.1083 +/- 0.3373 Interval 7, DeltaF=-1.5855 +/- 0.3873, Sum=9.1692 +/- 0.3488 Interval 8, DeltaF=-2.3721 +/- 0.3869, Sum=7.7641 +/- 0.3599 Interval 9, DeltaF=-2.8964 +/- 0.3364, Sum=6.0484 +/- 0.3661 Interval 10, DeltaF=-1.0163 +/- 0.1766, Sum=5.4465 +/- 0.3665 Forward EXP free energy: 5.4465 +/- 0.3665 Reverse EXP: Interval 1, DeltaF=6.4883 +/- 0.5691, Sum=3.8432 +/- 0.1919 Interval 2, DeltaF=1.9188 +/- 0.2899, Sum=4.9798 +/- 0.1982 Interval 3, DeltaF=3.1137 +/- 0.3458, Sum=6.8242 +/- 0.2105 Interval 4, DeltaF=3.4425 +/- 0.4101, Sum=8.8633 +/- 0.2329 Interval 5, DeltaF=1.4066 +/- 0.3990, Sum=9.6965 +/- 0.2512 Interval 6, DeltaF=-0.6665 +/- 0.3076, Sum=9.3017 +/- 0.2574 Interval 7, DeltaF=-1.5220 +/- 0.3966, Sum=8.4002 +/- 0.2738 Interval 8, DeltaF=-2.4692 +/- 0.3422, Sum=6.9376 +/- 0.2824 Interval 9, DeltaF=-2.8150 +/- 0.2980, Sum=5.2701 +/- 0.2873 Interval 10, DeltaF=-1.0939 +/- 0.1742, Sum=4.6222 +/- 0.2878 Reverse EXP free energy: 4.6222 +/- 0.2878 Averge of forward and reverse EXP: Interval 1, DeltaF=6.5077 +/- 0.2393, Sum=3.8548 +/- 0.0339 Interval 2, DeltaF=1.9438 +/- 0.0586, Sum=5.0062 +/- 0.0340 Interval 3, DeltaF=3.2689 +/- 0.1108, Sum=6.9425 +/- 0.0348 Interval 4, DeltaF=3.5984 +/- 0.1527, Sum=9.0739 +/- 0.0374 Interval 5, DeltaF=1.7051 +/- 0.1520, Sum=10.0839 +/- 0.0398 Interval 6, DeltaF=-0.6396 +/- 0.1805, Sum=9.7050 +/- 0.0442 Interval 7, DeltaF=-1.5538 +/- 0.1183, Sum=8.7847 +/- 0.0450 Interval 8, DeltaF=-2.4207 +/- 0.1034, Sum=7.3508 +/- 0.0455 Interval 9, DeltaF=-2.8557 +/- 0.0783, Sum=5.6593 +/- 0.0456 Interval 10, DeltaF=-1.0551 +/- 0.0237, Sum=5.0343 +/- 0.0456 Average EXP free energy: 5.0343 +/- 0.0456 Interval 1, DeltaF=6.4883 +/- 0.2493, Sum=3.8432 +/- 0.0368 Interval 2, DeltaF=1.9689 +/- 0.3278, Sum=5.0095 +/- 0.0735 Interval 3, DeltaF=3.1137 +/- 0.3757, Sum=6.8538 +/- 0.1113 Interval 4, DeltaF=3.7543 +/- 0.4149, Sum=9.0776 +/- 0.1510 Interval 5, DeltaF=1.4066 +/- 0.4451, Sum=9.9108 +/- 0.1912 Interval 6, DeltaF=-0.6128 +/- 0.5694, Sum=9.5478 +/- 0.2710 Interval 7, DeltaF=-1.5220 +/- 0.4883, Sum=8.6463 +/- 0.3056 Interval 8, DeltaF=-2.3721 +/- 0.6511, Sum=7.2412 +/- 0.3956 Interval 9, DeltaF=-2.8150 +/- 0.5234, Sum=5.5738 +/- 0.4275 Interval 10, DeltaF=-1.0163 +/- 0.6731, Sum=4.9718 +/- 0.5048 Double-Wide EXP free energy: 4.9718 +/- 0.5048 Method: BAR Interval 1, DeltaF=6.6751 +/- 0.3003, Sum=3.9539 +/- 0.0534 Interval 2, DeltaF=1.9868 +/- 0.2044, Sum=5.1308 +/- 0.0589 Interval 3, DeltaF=3.2278 +/- 0.2575, Sum=7.0427 +/- 0.0708 Interval 4, DeltaF=3.3278 +/- 0.2842, Sum=9.0139 +/- 0.0854 Interval 5, DeltaF=1.3682 +/- 0.2996, Sum=9.8243 +/- 0.1006 Interval 6, DeltaF=-0.5702 +/- 0.2353, Sum=9.4866 +/- 0.1058 Interval 7, DeltaF=-1.6960 +/- 0.2887, Sum=8.4820 +/- 0.1168 Interval 8, DeltaF=-2.3373 +/- 0.2743, Sum=7.0975 +/- 0.1250 Interval 9, DeltaF=-2.8649 +/- 0.2216, Sum=5.4005 +/- 0.1283 Interval 10, DeltaF=-1.0508 +/- 0.1449, Sum=4.7781 +/- 0.1289 BAR free energy: 4.7781 +/- 0.1289 Method: Unoptimized BAR -- assume initial free energies are zeroed Interval 1, DeltaF=6.5148 +/- 0.4273, Sum=3.8590 +/- 0.1082 Interval 2, DeltaF=1.9748 +/- 0.3063, Sum=5.0287 +/- 0.1216 Interval 3, DeltaF=3.2686 +/- 0.3012, Sum=6.9648 +/- 0.1330 Interval 4, DeltaF=3.2963 +/- 0.3636, Sum=8.9174 +/- 0.1543 Interval 5, DeltaF=1.3635 +/- 0.3405, Sum=9.7250 +/- 0.1689 Interval 6, DeltaF=-0.5937 +/- 0.2216, Sum=9.3733 +/- 0.1714 Interval 7, DeltaF=-1.6192 +/- 0.2340, Sum=8.4143 +/- 0.1744 Interval 8, DeltaF=-2.3964 +/- 0.3699, Sum=6.9948 +/- 0.1923 Interval 9, DeltaF=-2.8249 +/- 0.4470, Sum=5.3215 +/- 0.2258 Interval 10, DeltaF=-1.0665 +/- 0.2208, Sum=4.6898 +/- 0.2277 Unopt. BAR free energy: 4.6898 +/- 0.2277 Method: Postoptimized BAR -- compute for a range of initial dF, and choose the result where the input dF is closest to the output dF. Actually may require more iterations, but does not require self consistent solutions. Interval 1, DeltaF=6.6721 +/- 0.3057, Sum=3.9521 +/- 0.0554 Interval 2, DeltaF=1.9869 +/- 0.2040, Sum=5.1290 +/- 0.0606 Interval 3, DeltaF=3.2287 +/- 0.2559, Sum=7.0415 +/- 0.0720 Interval 4, DeltaF=3.3328 +/- 0.2931, Sum=9.0156 +/- 0.0881 Interval 5, DeltaF=1.3674 +/- 0.3104, Sum=9.8256 +/- 0.1050 Interval 6, DeltaF=-0.5513 +/- 0.2498, Sum=9.4990 +/- 0.1113 Interval 7, DeltaF=-1.7067 +/- 0.3027, Sum=8.4881 +/- 0.1238 Interval 8, DeltaF=-2.3432 +/- 0.2796, Sum=7.1001 +/- 0.1322 Interval 9, DeltaF=-2.8659 +/- 0.2132, Sum=5.4026 +/- 0.1349 Interval 10, DeltaF=-1.0516 +/- 0.1472, Sum=4.7797 +/- 0.1355 Postopt. BAR free energy: 4.7797 +/- 0.1355 Method: Pairwise MBAR. Should give identical results to BAR. Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 843 N_k = [343 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 3.49829079] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 4.85485403] relative max_delta = 2.794241e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 5.0280 relative max_delta = 3.443202e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 6.5895 relative max_delta = 2.369680e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6746 relative max_delta = 1.275825e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6751 relative max_delta = 7.250096e-05 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6751 relative max_delta = 2.360460e-09 Converged to tolerance of 2.360460e-09 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6751 Final dimensionless free energies f_k = [ 0. 6.67511182] Computing normalized weights... Interval 1, DeltaF=6.6751 +/- 0.3003, Sum=3.9539 +/- 0.0534 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 819 N_k = [500 319] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.57902687] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.88650025] relative max_delta = 1.629861e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8966 relative max_delta = 5.326577e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.9874 relative max_delta = 4.567958e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.9868 relative max_delta = 2.776100e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.9868 relative max_delta = 9.260271e-09 Converged to tolerance of 9.260271e-09 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.9868 Final dimensionless free energies f_k = [ 0. 1.98683399] Computing normalized weights... Interval 2, DeltaF=1.9868 +/- 0.2044, Sum=5.1308 +/- 0.0589 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 819 N_k = [319 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 1.67159755] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 2.48424753] relative max_delta = 3.271212e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 2.5584 relative max_delta = 2.897783e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.2248 relative max_delta = 2.066542e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.2278 relative max_delta = 9.269724e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.2278 relative max_delta = 9.102414e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.2278 relative max_delta = 8.254969e-16 Converged to tolerance of 8.254969e-16 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.2278 Final dimensionless free energies f_k = [ 0. 3.22779553] Computing normalized weights... Interval 3, DeltaF=3.2278 +/- 0.2575, Sum=7.0427 +/- 0.0708 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.947581] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 1.66812903] relative max_delta = 4.319498e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 1.8714 relative max_delta = 1.086368e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 3.6144 relative max_delta = 4.822312e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 3.3366 relative max_delta = 8.326610e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 2.639715e-03 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 2.666595e-06 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 3.3278 relative max_delta = 2.721808e-12 Converged to tolerance of 2.721808e-12 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 3.3278 Final dimensionless free energies f_k = [ 0. 3.32780458] Computing normalized weights... Interval 4, DeltaF=3.3278 +/- 0.2842, Sum=9.0139 +/- 0.0854 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 1000 N_k = [500 500] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 0.38465576] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 0.67370076] relative max_delta = 4.290406e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 0.7501 relative max_delta = 1.018851e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 1.4229 relative max_delta = 4.728036e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 1.3685 relative max_delta = 3.969354e-02 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 1.3682 relative max_delta = 2.756581e-04 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 1.3682 relative max_delta = 1.327221e-08 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 1.3682 relative max_delta = 4.057351e-15 Converged to tolerance of 4.057351e-15 in 6 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 1.3682 Final dimensionless free energies f_k = [ 0. 1.36816243] Computing normalized weights... Interval 5, DeltaF=1.3682 +/- 0.2996, Sum=9.8243 +/- 0.1006 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 850 N_k = [500 350] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.35906502] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -0.48973085] relative max_delta = 2.668115e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -0.4977 relative max_delta = 1.603882e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -0.5697 relative max_delta = 1.263151e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -0.5702 relative max_delta = 8.793636e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -0.5702 relative max_delta = 4.398177e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -0.5702 relative max_delta = 2.336602e-15 Converged to tolerance of 2.336602e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -0.5702 Final dimensionless free energies f_k = [ 0. -0.57017315] Computing normalized weights... Interval 6, DeltaF=-0.5702 +/- 0.2353, Sum=9.4866 +/- 0.1058 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 510 N_k = [350 160] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.03021591] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.41675417] relative max_delta = 2.728337e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.4437 relative max_delta = 1.866924e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.6880 relative max_delta = 1.447198e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.6960 relative max_delta = 4.710374e-03 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.6960 relative max_delta = 5.129180e-06 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -1.6960 relative max_delta = 6.082826e-12 Converged to tolerance of 6.082826e-12 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.6960 Final dimensionless free energies f_k = [ 0. -1.69599051] Computing normalized weights... Interval 7, DeltaF=-1.6960 +/- 0.2887, Sum=8.4820 +/- 0.1168 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 339 N_k = [160 179] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -1.65134625] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.11606288] relative max_delta = 2.196138e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.1384 relative max_delta = 1.042941e-02 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.3387 relative max_delta = 8.565781e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.3373 relative max_delta = 5.915508e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.3373 relative max_delta = 1.922314e-08 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.3373 relative max_delta = 0.000000e+00 Converged to tolerance of 0.000000e+00 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.3373 Final dimensionless free energies f_k = [ 0. -2.33730931] Computing normalized weights... Interval 8, DeltaF=-2.3373 +/- 0.2743, Sum=7.0975 +/- 0.1250 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 543 N_k = [179 364] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -2.34377205] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -2.74929452] relative max_delta = 1.475006e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -2.7610 relative max_delta = 4.255465e-03 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -2.8664 relative max_delta = 3.676203e-02 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -2.8649 relative max_delta = 5.204754e-04 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -2.8649 relative max_delta = 1.001297e-07 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 -2.8649 relative max_delta = 2.945168e-15 Converged to tolerance of 2.945168e-15 in 5 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -2.8649 Final dimensionless free energies f_k = [ 0. -2.86492802] Computing normalized weights... Interval 9, DeltaF=-2.8649 +/- 0.2216, Sum=5.4005 +/- 0.1283 Using embedded C++ helper code. K = 2, L = 2, N_max = 500, total samples = 811 N_k = [364 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. -0.96875728] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. -1.04414308] relative max_delta = 7.219873e-02 Determining dimensionless free energies by Newton-Raphson iteration. There are 2 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 -1.0448 relative max_delta = 6.387219e-04 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 -1.0508 relative max_delta = 5.715246e-03 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 -1.0508 relative max_delta = 1.675697e-06 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 -1.0508 relative max_delta = 1.466472e-13 Converged to tolerance of 1.466472e-13 in 4 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 -1.0508 Final dimensionless free energies f_k = [ 0. -1.05081433] Computing normalized weights... Interval 10, DeltaF=-1.0508 +/- 0.1449, Sum=4.7781 +/- 0.1289 Pairwise MBAR free energy: 4.7781 +/- 0.1289 Method: Full-state MBAR Using embedded C++ helper code. K = 11, L = 11, N_max = 500, total samples = 4162 N_k = [343 500 319 500 500 500 350 160 179 364 447] Initializing free energies to zero. Initial dimensionless free energies f_k = [ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.] MBAR: Computing dimensionless free energies by iteration. This may take from seconds to minutes, depending on the quantity of data... Self-consistent iteration 0 current f_k = [ 0. 2.02096415 2.02448325 1.92637246 1.64758946 1.81243875 1.76236512 1.74633938 1.7315552 1.20750592 0.74046543] relative max_delta = 1.000000e+00 Self-consistent iteration 1 current f_k = [ 0. 3.04527991 3.40562195 3.46852585 3.0509093 3.2740408 3.1990946 3.09923914 2.92341631 1.9778685 1.34241884] relative max_delta = 4.446135e-01 Determining dimensionless free energies by Newton-Raphson iteration. There are 11 states with samples. Newton-Raphson iteration 0 current f_k for states with samples = 0.0000 3.3118 3.8073 4.3207 4.4787 4.8349 4.7189 4.5148 4.1820 3.0100 2.3256 relative max_delta = 3.228382e-01 Newton-Raphson iteration 1 current f_k for states with samples = 0.0000 5.8520 7.6066 11.7277 16.6616 18.1689 17.6740 16.4623 14.5818 11.3622 10.2531 relative max_delta = 7.338888e-01 Newton-Raphson iteration 2 current f_k for states with samples = 0.0000 6.6236 8.7058 11.9129 15.6141 16.9598 16.4111 14.7374 12.4381 9.5055 8.4561 relative max_delta = 1.263944e-01 Newton-Raphson iteration 3 current f_k for states with samples = 0.0000 6.6642 8.6386 11.8819 15.2418 16.5827 16.0265 14.3261 11.9814 9.0895 8.0380 relative max_delta = 2.754380e-02 Newton-Raphson iteration 4 current f_k for states with samples = 0.0000 6.6636 8.6382 11.8786 15.2228 16.5642 16.0079 14.3075 11.9622 9.0708 8.0194 relative max_delta = 1.158190e-03 Newton-Raphson iteration 5 current f_k for states with samples = 0.0000 6.6636 8.6382 11.8786 15.2228 16.5642 16.0079 14.3074 11.9622 9.0708 8.0193 relative max_delta = 2.548898e-06 Newton-Raphson iteration 6 current f_k for states with samples = 0.0000 6.6636 8.6382 11.8786 15.2228 16.5642 16.0079 14.3074 11.9622 9.0708 8.0193 relative max_delta = 1.334120e-11 Converged to tolerance of 1.334120e-11 in 7 Newton-Raphson iterations. Recomputing all free energies... current f_k for all states = 0.0000 6.6636 8.6382 11.8786 15.2228 16.5642 16.0079 14.3074 11.9622 9.0708 8.0193 Final dimensionless free energies f_k = [ 0. 6.66362984 8.63815141 11.87856626 15.22280618 16.56416791 16.00788122 14.3074139 11.96217071 9.07080764 8.01931315] Computing normalized weights... DeltaMij: [[ 0. 3.94711681 5.11669967 7.0361184 9.01703659 9.81157524 9.48206586 8.47481556 7.08564044 5.37297811 4.75013866] [-3.94711681 0. 1.16958287 3.08900159 5.06991979 5.86445844 5.53494905 4.52769875 3.13852363 1.42586131 0.80302185] [-5.11669967 -1.16958287 0. 1.91941873 3.90033692 4.69487557 4.36536618 3.35811589 1.96894076 0.25627844 -0.36656102] [-7.0361184 -3.08900159 -1.91941873 0. 1.98091819 2.77545684 2.44594746 1.43869716 0.04952204 -1.66314028 -2.28597974] [-9.01703659 -5.06991979 -3.90033692 -1.98091819 0. 0.79453865 0.46502927 -0.54222103 -1.93139616 -3.64405848 -4.26689794] [-9.81157524 -5.86445844 -4.69487557 -2.77545684 -0.79453865 0. -0.32950939 -1.33675968 -2.72593481 -4.43859713 -5.06143659] [-9.48206586 -5.53494905 -4.36536618 -2.44594746 -0.46502927 0.32950939 0. -1.0072503 -2.39642542 -4.10908774 -4.7319272 ] [-8.47481556 -4.52769875 -3.35811589 -1.43869716 0.54222103 1.33675968 1.0072503 0. -1.38917513 -3.10183745 -3.7246769 ] [-7.08564044 -3.13852363 -1.96894076 -0.04952204 1.93139616 2.72593481 2.39642542 1.38917513 0. -1.71266232 -2.33550178] [-5.37297811 -1.42586131 -0.25627844 1.66314028 3.64405848 4.43859713 4.10908774 3.10183745 1.71266232 0. -0.62283946] [-4.75013866 -0.80302185 0.36656102 2.28597974 4.26689794 5.06143659 4.7319272 3.7246769 2.33550178 0.62283946 0. ]] dDeltaMij: [[ 0. 0.05281069 0.06539728 0.07883377 0.09474687 0.11327564 0.121682 0.13531309 0.14855116 0.15564499 0.15776005] [ 0.05281069 0. 0.02329723 0.04879947 0.07176873 0.09489614 0.10478747 0.12034756 0.13506055 0.14282599 0.145128 ] [ 0.06539728 0.02329723 0. 0.03472213 0.06339493 0.08873396 0.09924136 0.11555073 0.13080439 0.13880814 0.14117568] [ 0.07883377 0.04879947 0.03472213 0. 0.04619598 0.07733868 0.08919934 0.10704969 0.12335904 0.13181565 0.13430651] [ 0.09474687 0.07176873 0.06339493 0.04619598 0. 0.05224344 0.06854916 0.09056808 0.10936337 0.11882029 0.12157769] [ 0.11327564 0.09489614 0.08873396 0.07733868 0.05224344 0. 0.03151943 0.06673916 0.09064609 0.10185401 0.10505751] [ 0.121682 0.10478747 0.09924136 0.08919934 0.06854916 0.03151943 0. 0.04680437 0.07653426 0.08957884 0.09320759] [ 0.13531309 0.12034756 0.11555073 0.10704969 0.09056808 0.06673916 0.04680437 0. 0.03867355 0.05790419 0.06338107] [ 0.14855116 0.13506055 0.13080439 0.12335904 0.10936337 0.09064609 0.07653426 0.03867355 0. 0.02443539 0.03322603] [ 0.15564499 0.14282599 0.13880814 0.13181565 0.11882029 0.10185401 0.08957884 0.05790419 0.02443539 0. 0.01141521] [ 0.15776005 0.145128 0.14117568 0.13430651 0.12157769 0.10505751 0.09320759 0.06338107 0.03322603 0.01141521 0. ]] ========== Average EXP ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.009083 ( 0.005559, 0.013448) 0.079656 0.2 -24.000000 0.016803 ( 0.011863, 0.022573) 0.158519 0.3 -10.111111 0.023161 ( 0.017300, 0.029841) 0.235823 0.4 -5.250000 0.026794 ( 0.020467, 0.033934) 0.310843 0.5 -3.000000 0.032698 ( 0.025682, 0.040517) 0.382925 0.6 -1.777778 0.037693 ( 0.030146, 0.046035) 0.451494 0.7 -1.040816 0.042688 ( 0.034648, 0.051516) 0.516073 0.8 -0.562500 0.049046 ( 0.040423, 0.058445) 0.576289 0.9 -0.234568 0.054496 ( 0.045407, 0.064351) 0.631880 1.0 -0.000000 0.061762 ( 0.052093, 0.072185) 0.682689 1.1 0.173554 0.068120 ( 0.057976, 0.079006) 0.728668 1.2 0.305556 0.074478 ( 0.063886, 0.085802) 0.769861 1.3 0.408284 0.079927 ( 0.068970, 0.091607) 0.806399 1.4 0.489796 0.086285 ( 0.074921, 0.098361) 0.838487 1.5 0.555556 0.094914 ( 0.083028, 0.107496) 0.866386 1.6 0.609375 0.101726 ( 0.089450, 0.114687) 0.890401 1.7 0.653979 0.108084 ( 0.095460, 0.121381) 0.910869 1.8 0.691358 0.116712 ( 0.103639, 0.130445) 0.928139 1.9 0.722992 0.123070 ( 0.109680, 0.137108) 0.942567 2.0 0.750000 0.128974 ( 0.115301, 0.143285) 0.954500 2.1 0.773243 0.133515 ( 0.119631, 0.148029) 0.964271 2.2 0.793388 0.140781 ( 0.126571, 0.155610) 0.972193 2.3 0.810964 0.145322 ( 0.130915, 0.160340) 0.978552 2.4 0.826389 0.151680 ( 0.137005, 0.166955) 0.983605 2.5 0.840000 0.157130 ( 0.142232, 0.172618) 0.987581 2.6 0.852071 0.161671 ( 0.146593, 0.177332) 0.990678 2.7 0.862826 0.167121 ( 0.151831, 0.182983) 0.993066 2.8 0.872449 0.176203 ( 0.160576, 0.192388) 0.994890 2.9 0.881094 0.184832 ( 0.168897, 0.201309) 0.996268 3.0 0.888889 0.191190 ( 0.175038, 0.207873) 0.997300 3.1 0.895942 0.196639 ( 0.180306, 0.213494) 0.998065 3.2 0.902344 0.202997 ( 0.186459, 0.220046) 0.998626 3.3 0.908173 0.209809 ( 0.193059, 0.227059) 0.999033 3.4 0.913495 0.214805 ( 0.197904, 0.232197) 0.999326 3.5 0.918367 0.220254 ( 0.203193, 0.237797) 0.999535 3.6 0.922840 0.228883 ( 0.211576, 0.246656) 0.999682 3.7 0.926954 0.237057 ( 0.219527, 0.255039) 0.999784 3.8 0.930748 0.243869 ( 0.226161, 0.262018) 0.999855 3.9 0.934254 0.251135 ( 0.233243, 0.269456) 0.999904 4.0 0.937500 0.257493 ( 0.239446, 0.275958) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0151 0.0167 0.1620 0.1611 2 5.1681 0.0175 0.1725 0.1716 3 7.1082 0.0474 0.2136 0.2083 4 9.2553 0.2181 0.3221 0.2370 5 10.1503 0.4200 0.4782 0.2287 6 9.8378 0.4162 0.4832 0.2456 7 8.8471 0.3799 0.4715 0.2793 8 7.4690 0.3574 0.4506 0.2744 9 5.7404 0.3432 0.4475 0.2872 10 5.1042 0.3438 0.4513 0.2923 Last line is the total ========== BAR ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.051317 ( 0.042496, 0.060909) 0.079656 0.2 -24.000000 0.112171 ( 0.099331, 0.125678) 0.158519 0.3 -10.111111 0.176203 ( 0.160576, 0.192388) 0.235823 0.4 -5.250000 0.227975 ( 0.210693, 0.245724) 0.310843 0.5 -3.000000 0.283833 ( 0.265194, 0.302843) 0.382925 0.6 -1.777778 0.331063 ( 0.311559, 0.350857) 0.451494 0.7 -1.040816 0.391462 ( 0.371177, 0.411935) 0.516073 0.8 -0.562500 0.444142 ( 0.423443, 0.464936) 0.576289 0.9 -0.234568 0.483197 ( 0.462346, 0.504077) 0.631880 1.0 -0.000000 0.537239 ( 0.516388, 0.558026) 0.682689 1.1 0.173554 0.581744 ( 0.561077, 0.602270) 0.728668 1.2 0.305556 0.619437 ( 0.599062, 0.639607) 0.769861 1.3 0.408284 0.654859 ( 0.634876, 0.674576) 0.806399 1.4 0.489796 0.691190 ( 0.671735, 0.710315) 0.838487 1.5 0.555556 0.720708 ( 0.701786, 0.739251) 0.866386 1.6 0.609375 0.749319 ( 0.731009, 0.767200) 0.890401 1.7 0.653979 0.787466 ( 0.770138, 0.804299) 0.910869 1.8 0.691358 0.816076 ( 0.799630, 0.831979) 0.928139 1.9 0.722992 0.839237 ( 0.823611, 0.854280) 0.942567 2.0 0.750000 0.858311 ( 0.843444, 0.872561) 0.954500 2.1 0.773243 0.876930 ( 0.862892, 0.890320) 0.964271 2.2 0.793388 0.893279 ( 0.880052, 0.905829) 0.972193 2.3 0.810964 0.908265 ( 0.895866, 0.919963) 0.978552 2.4 0.826389 0.920527 ( 0.908876, 0.931454) 0.983605 2.5 0.840000 0.932334 ( 0.921480, 0.942445) 0.987581 2.6 0.852071 0.941871 ( 0.931727, 0.951255) 0.990678 2.7 0.862826 0.950045 ( 0.940568, 0.958748) 0.993066 2.8 0.872449 0.956403 ( 0.947492, 0.964530) 0.994890 2.9 0.881094 0.961853 ( 0.953465, 0.969447) 0.996268 3.0 0.888889 0.965486 ( 0.957472, 0.972700) 0.997300 3.1 0.895942 0.971390 ( 0.964033, 0.977936) 0.998065 3.2 0.902344 0.975477 ( 0.968620, 0.981517) 0.998626 3.3 0.908173 0.981381 ( 0.975334, 0.986600) 0.999033 3.4 0.913495 0.983651 ( 0.977953, 0.988519) 0.999326 3.5 0.918367 0.986376 ( 0.981132, 0.990785) 0.999535 3.6 0.922840 0.989101 ( 0.984361, 0.993001) 0.999682 3.7 0.926954 0.990917 ( 0.986552, 0.994441) 0.999784 3.8 0.930748 0.993642 ( 0.989921, 0.996518) 0.999855 3.9 0.934254 0.994550 ( 0.991075, 0.997180) 0.999904 4.0 0.937500 0.996821 ( 0.994076, 0.998720) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 3.9988 0.0005 0.0511 0.0511 2 5.1554 0.0047 0.0666 0.0664 3 7.0734 0.0127 0.0895 0.0886 4 9.0800 0.0427 0.1176 0.1096 5 9.8080 0.0777 0.1625 0.1427 6 9.4826 0.0610 0.1649 0.1532 7 8.5017 0.0345 0.1674 0.1638 8 7.1276 0.0161 0.1656 0.1648 9 5.4013 0.0042 0.1686 0.1686 10 4.7639 0.0035 0.1747 0.1747 Last line is the total ========== Reverse EXP ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.071753 ( 0.061350, 0.082892) 0.079656 0.2 -24.000000 0.140781 ( 0.126571, 0.155610) 0.158519 0.3 -10.111111 0.205268 ( 0.188659, 0.222384) 0.235823 0.4 -5.250000 0.279746 ( 0.261194, 0.298677) 0.310843 0.5 -3.000000 0.359219 ( 0.339308, 0.379372) 0.382925 0.6 -1.777778 0.414623 ( 0.394126, 0.435267) 0.451494 0.7 -1.040816 0.476839 ( 0.456005, 0.497714) 0.516073 0.8 -0.562500 0.525886 ( 0.505014, 0.546712) 0.576289 0.9 -0.234568 0.570845 ( 0.550117, 0.591450) 0.631880 1.0 -0.000000 0.617166 ( 0.596770, 0.637361) 0.682689 1.1 0.173554 0.661217 ( 0.641317, 0.680840) 0.728668 1.2 0.305556 0.701635 ( 0.682358, 0.720565) 0.769861 1.3 0.408284 0.741144 ( 0.722649, 0.759225) 0.806399 1.4 0.489796 0.772025 ( 0.754276, 0.789307) 0.838487 1.5 0.555556 0.797457 ( 0.780422, 0.813980) 0.866386 1.6 0.609375 0.826975 ( 0.810902, 0.842487) 0.890401 1.7 0.653979 0.850590 ( 0.835406, 0.865172) 0.910869 1.8 0.691358 0.870572 ( 0.856240, 0.884266) 0.928139 1.9 0.722992 0.894641 ( 0.881486, 0.907118) 0.942567 2.0 0.750000 0.913715 ( 0.901639, 0.925079) 0.954500 2.1 0.773243 0.926431 ( 0.915168, 0.936960) 0.964271 2.2 0.793388 0.939600 ( 0.929281, 0.949164) 0.972193 2.3 0.810964 0.951408 ( 0.942048, 0.959991) 0.978552 2.4 0.826389 0.958674 ( 0.949976, 0.966583) 0.983605 2.5 0.840000 0.964578 ( 0.956468, 0.971889) 0.987581 2.6 0.852071 0.969119 ( 0.961501, 0.975931) 0.990678 2.7 0.862826 0.973660 ( 0.966576, 0.979931) 0.993066 2.8 0.872449 0.978202 ( 0.971704, 0.983878) 0.994890 2.9 0.881094 0.981381 ( 0.975334, 0.986600) 0.996268 3.0 0.888889 0.983197 ( 0.977427, 0.988137) 0.997300 3.1 0.895942 0.985014 ( 0.979537, 0.989657) 0.998065 3.2 0.902344 0.988193 ( 0.983278, 0.992269) 0.998626 3.3 0.908173 0.988647 ( 0.983819, 0.992636) 0.999033 3.4 0.913495 0.990009 ( 0.985452, 0.993726) 0.999326 3.5 0.918367 0.990463 ( 0.986001, 0.994084) 0.999535 3.6 0.922840 0.991371 ( 0.987106, 0.994795) 0.999682 3.7 0.926954 0.992280 ( 0.988222, 0.995494) 0.999784 3.8 0.930748 0.993188 ( 0.989351, 0.996181) 0.999855 3.9 0.934254 0.993188 ( 0.989351, 0.996181) 0.999904 4.0 0.937500 0.995005 ( 0.991660, 0.997503) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0125 0.0141 0.2830 0.2827 2 5.1745 0.0239 0.2870 0.2860 3 7.0820 0.0213 0.3139 0.3132 4 9.1033 0.0661 0.3114 0.3043 5 9.8079 0.0776 0.3325 0.3233 6 9.4801 0.0585 0.3243 0.3189 7 8.4860 0.0187 0.3347 0.3342 8 7.1055 -0.0061 0.3478 0.3478 9 5.3733 -0.0239 0.3534 0.3526 10 4.7386 -0.0218 0.3567 0.3560 Last line is the total ========== Double-Wide ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.116712 ( 0.103639, 0.130445) 0.079656 0.2 -24.000000 0.208447 ( 0.191739, 0.225657) 0.158519 0.3 -10.111111 0.306085 ( 0.287010, 0.325495) 0.235823 0.4 -5.250000 0.388283 ( 0.368030, 0.408729) 0.310843 0.5 -3.000000 0.455041 ( 0.434287, 0.475872) 0.382925 0.6 -1.777778 0.506358 ( 0.485477, 0.527228) 0.451494 0.7 -1.040816 0.551317 ( 0.530506, 0.572040) 0.516073 0.8 -0.562500 0.596276 ( 0.575707, 0.616680) 0.576289 0.9 -0.234568 0.629428 ( 0.609151, 0.649482) 0.631880 1.0 -0.000000 0.658946 ( 0.639016, 0.678603) 0.682689 1.1 0.173554 0.689827 ( 0.670351, 0.708978) 0.728668 1.2 0.305556 0.711172 ( 0.692067, 0.729913) 0.769861 1.3 0.408284 0.733878 ( 0.715226, 0.752129) 0.806399 1.4 0.489796 0.759310 ( 0.741238, 0.776936) 0.838487 1.5 0.555556 0.775204 ( 0.757539, 0.792397) 0.866386 1.6 0.609375 0.790645 ( 0.773409, 0.807381) 0.890401 1.7 0.653979 0.806085 ( 0.789316, 0.822329) 0.910869 1.8 0.691358 0.821526 ( 0.805263, 0.837236) 0.928139 1.9 0.722992 0.836058 ( 0.820313, 0.851225) 0.942567 2.0 0.750000 0.848774 ( 0.833517, 0.863431) 0.954500 2.1 0.773243 0.857856 ( 0.842971, 0.872127) 0.964271 2.2 0.793388 0.863760 ( 0.849126, 0.877768) 0.972193 2.3 0.810964 0.870572 ( 0.856240, 0.884266) 0.978552 2.4 0.826389 0.873751 ( 0.859565, 0.887295) 0.983605 2.5 0.840000 0.883288 ( 0.869555, 0.896361) 0.987581 2.6 0.852071 0.890554 ( 0.877186, 0.903250) 0.990678 2.7 0.862826 0.894187 ( 0.881008, 0.906688) 0.993066 2.8 0.872449 0.902361 ( 0.889625, 0.914405) 0.994890 2.9 0.881094 0.905540 ( 0.892984, 0.917400) 0.996268 3.0 0.888889 0.909173 ( 0.896827, 0.920816) 0.997300 3.1 0.895942 0.911898 ( 0.899713, 0.923375) 0.998065 3.2 0.902344 0.915531 ( 0.903567, 0.926781) 0.998626 3.3 0.908173 0.918710 ( 0.906944, 0.929756) 0.999033 3.4 0.913495 0.920981 ( 0.909359, 0.931878) 0.999326 3.5 0.918367 0.925522 ( 0.914198, 0.936114) 0.999535 3.6 0.922840 0.930972 ( 0.920021, 0.941181) 0.999682 3.7 0.926954 0.935513 ( 0.924888, 0.945389) 0.999784 3.8 0.930748 0.937784 ( 0.927327, 0.947488) 0.999855 3.9 0.934254 0.940963 ( 0.930748, 0.950419) 0.999904 4.0 0.937500 0.942325 ( 0.932216, 0.951673) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0125 0.0141 0.2830 0.2827 2 5.1565 0.0058 0.3018 0.3017 3 7.0640 0.0032 0.3348 0.3347 4 9.3370 0.2997 0.5047 0.4060 5 10.0415 0.3113 0.5256 0.4235 6 9.7442 0.3226 0.5349 0.4266 7 8.7501 0.2828 0.5293 0.4474 8 7.3743 0.2627 0.5272 0.4571 9 5.6421 0.2449 0.5218 0.4607 10 5.0045 0.2441 0.5243 0.4640 Last line is the total ========== Unopt. BAR ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.083560 ( 0.072368, 0.095469) 0.079656 0.2 -24.000000 0.157584 ( 0.142668, 0.173090) 0.158519 0.3 -10.111111 0.227975 ( 0.210693, 0.245724) 0.235823 0.4 -5.250000 0.282470 ( 0.263861, 0.301455) 0.310843 0.5 -3.000000 0.349228 ( 0.329453, 0.369263) 0.382925 0.6 -1.777778 0.408719 ( 0.388272, 0.429324) 0.451494 0.7 -1.040816 0.464124 ( 0.443331, 0.484978) 0.516073 0.8 -0.562500 0.514986 ( 0.494106, 0.535841) 0.576289 0.9 -0.234568 0.564487 ( 0.543729, 0.585134) 0.631880 1.0 -0.000000 0.615350 ( 0.594937, 0.635564) 0.682689 1.1 0.173554 0.656676 ( 0.636716, 0.676366) 0.728668 1.2 0.305556 0.697548 ( 0.678200, 0.716556) 0.769861 1.3 0.408284 0.742053 ( 0.723578, 0.760111) 0.806399 1.4 0.489796 0.773842 ( 0.756140, 0.791073) 0.838487 1.5 0.555556 0.798819 ( 0.781825, 0.815299) 0.866386 1.6 0.609375 0.826067 ( 0.809962, 0.841612) 0.890401 1.7 0.653979 0.847411 ( 0.832100, 0.862125) 0.910869 1.8 0.691358 0.868756 ( 0.854342, 0.882535) 0.928139 1.9 0.722992 0.888738 ( 0.875276, 0.901530) 0.942567 2.0 0.750000 0.907811 ( 0.895385, 0.919536) 0.954500 2.1 0.773243 0.924614 ( 0.913230, 0.935268) 0.964271 2.2 0.793388 0.938692 ( 0.928304, 0.948326) 0.972193 2.3 0.810964 0.945958 ( 0.936140, 0.955010) 0.978552 2.4 0.826389 0.954587 ( 0.945509, 0.962883) 0.983605 2.5 0.840000 0.964578 ( 0.956468, 0.971889) 0.987581 2.6 0.852071 0.972298 ( 0.965048, 0.978736) 0.990678 2.7 0.862826 0.975023 ( 0.968108, 0.981121) 0.993066 2.8 0.872449 0.979110 ( 0.972737, 0.984659) 0.994890 2.9 0.881094 0.982743 ( 0.976903, 0.987754) 0.996268 3.0 0.888889 0.987284 ( 0.982202, 0.991530) 0.997300 3.1 0.895942 0.989101 ( 0.984361, 0.993001) 0.998065 3.2 0.902344 0.990463 ( 0.986001, 0.994084) 0.998626 3.3 0.908173 0.991371 ( 0.987106, 0.994795) 0.999033 3.4 0.913495 0.993188 ( 0.989351, 0.996181) 0.999326 3.5 0.918367 0.993642 ( 0.989921, 0.996518) 0.999535 3.6 0.922840 0.994096 ( 0.990496, 0.996851) 0.999682 3.7 0.926954 0.995005 ( 0.991660, 0.997503) 0.999784 3.8 0.930748 0.995005 ( 0.991660, 0.997503) 0.999855 3.9 0.934254 0.995913 ( 0.992851, 0.998129) 0.999904 4.0 0.937500 0.996367 ( 0.993458, 0.998430) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0074 0.0091 0.1682 0.1679 2 5.1581 0.0074 0.1649 0.1647 3 7.0862 0.0255 0.1985 0.1969 4 9.0845 0.0472 0.2403 0.2356 5 9.8142 0.0839 0.2589 0.2449 6 9.4883 0.0667 0.2580 0.2492 7 8.5037 0.0365 0.2680 0.2655 8 7.1257 0.0141 0.2745 0.2741 9 5.3961 -0.0011 0.2820 0.2820 10 4.7594 -0.0010 0.2886 0.2886 Last line is the total ========== Forward EXP ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.033152 ( 0.026086, 0.041020) 0.079656 0.2 -24.000000 0.057675 ( 0.048327, 0.067784) 0.158519 0.3 -10.111111 0.087193 ( 0.075773, 0.099324) 0.235823 0.4 -5.250000 0.128974 ( 0.115301, 0.143285) 0.310843 0.5 -3.000000 0.163942 ( 0.148775, 0.179687) 0.382925 0.6 -1.777778 0.201635 ( 0.185140, 0.218643) 0.451494 0.7 -1.040816 0.238874 ( 0.221296, 0.256901) 0.516073 0.8 -0.562500 0.275204 ( 0.256750, 0.294045) 0.576289 0.9 -0.234568 0.304723 ( 0.285673, 0.324109) 0.631880 1.0 -0.000000 0.330609 ( 0.311112, 0.350396) 0.682689 1.1 0.173554 0.361490 ( 0.341549, 0.381668) 0.728668 1.2 0.305556 0.392371 ( 0.372076, 0.412851) 0.769861 1.3 0.408284 0.427793 ( 0.407197, 0.448513) 0.806399 1.4 0.489796 0.455495 ( 0.434739, 0.476327) 0.838487 1.5 0.555556 0.485468 ( 0.464612, 0.506348) 0.866386 1.6 0.609375 0.506358 ( 0.485477, 0.527228) 0.890401 1.7 0.653979 0.534514 ( 0.513657, 0.555312) 0.910869 1.8 0.691358 0.555858 ( 0.535064, 0.576557) 0.928139 1.9 0.722992 0.580381 ( 0.559707, 0.600918) 0.942567 2.0 0.750000 0.598547 ( 0.577995, 0.618929) 0.954500 2.1 0.773243 0.608992 ( 0.588523, 0.629273) 0.964271 2.2 0.793388 0.625795 ( 0.605481, 0.645892) 0.972193 2.3 0.810964 0.635786 ( 0.615577, 0.655761) 0.978552 2.4 0.826389 0.656222 ( 0.636256, 0.675919) 0.983605 2.5 0.840000 0.673025 ( 0.653289, 0.692462) 0.987581 2.6 0.852071 0.684378 ( 0.664814, 0.703625) 0.990678 2.7 0.862826 0.702089 ( 0.682820, 0.721010) 0.993066 2.8 0.872449 0.719800 ( 0.700860, 0.738362) 0.994890 2.9 0.881094 0.742507 ( 0.724042, 0.760554) 0.996268 3.0 0.888889 0.761580 ( 0.743564, 0.779146) 0.997300 3.1 0.895942 0.780200 ( 0.762669, 0.797248) 0.998065 3.2 0.902344 0.796094 ( 0.779018, 0.812661) 0.998626 3.3 0.908173 0.811081 ( 0.794470, 0.827156) 0.999033 3.4 0.913495 0.818801 ( 0.802446, 0.834608) 0.999326 3.5 0.918367 0.829700 ( 0.813723, 0.845110) 0.999535 3.6 0.922840 0.840145 ( 0.824553, 0.855152) 0.999682 3.7 0.926954 0.852861 ( 0.837769, 0.867346) 0.999784 3.8 0.930748 0.860581 ( 0.845811, 0.874732) 0.999855 3.9 0.934254 0.866939 ( 0.852445, 0.880802) 0.999904 4.0 0.937500 0.876476 ( 0.862416, 0.889888) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0177 0.0194 0.1947 0.1938 2 5.1617 0.0111 0.1912 0.1909 3 7.1343 0.0736 0.2953 0.2859 4 9.4073 0.3701 0.5028 0.3403 5 10.4927 0.7624 0.8531 0.3827 6 10.1954 0.7738 0.8838 0.4271 7 9.2083 0.7410 0.8874 0.4881 8 7.8325 0.7210 0.8634 0.4751 9 6.1074 0.7102 0.8677 0.4985 10 5.4698 0.7094 0.8706 0.5047 Last line is the total ========== Postopt. BAR ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.055858 ( 0.046657, 0.065823) 0.079656 0.2 -24.000000 0.120345 ( 0.107089, 0.134254) 0.158519 0.3 -10.111111 0.183015 ( 0.167144, 0.199432) 0.235823 0.4 -5.250000 0.238874 ( 0.221296, 0.256901) 0.310843 0.5 -3.000000 0.289737 ( 0.270977, 0.308858) 0.382925 0.6 -1.777778 0.342870 ( 0.323186, 0.362824) 0.451494 0.7 -1.040816 0.403270 ( 0.382870, 0.423835) 0.516073 0.8 -0.562500 0.458674 ( 0.437904, 0.479515) 0.576289 0.9 -0.234568 0.502725 ( 0.481846, 0.523599) 0.631880 1.0 -0.000000 0.548138 ( 0.527317, 0.568877) 0.682689 1.1 0.173554 0.590827 ( 0.570219, 0.611278) 0.728668 1.2 0.305556 0.638056 ( 0.617872, 0.658003) 0.769861 1.3 0.408284 0.673479 ( 0.653750, 0.692909) 0.806399 1.4 0.489796 0.702997 ( 0.683744, 0.721901) 0.838487 1.5 0.555556 0.738420 ( 0.719865, 0.756564) 0.866386 1.6 0.609375 0.772934 ( 0.755208, 0.790190) 0.890401 1.7 0.653979 0.801090 ( 0.784165, 0.817497) 0.910869 1.8 0.691358 0.830609 ( 0.814664, 0.845984) 0.928139 1.9 0.722992 0.852861 ( 0.837769, 0.867346) 0.942567 2.0 0.750000 0.871935 ( 0.857665, 0.885565) 0.954500 2.1 0.773243 0.891462 ( 0.878141, 0.904110) 0.964271 2.2 0.793388 0.900091 ( 0.887229, 0.912264) 0.972193 2.3 0.810964 0.911898 ( 0.899713, 0.923375) 0.978552 2.4 0.826389 0.924160 ( 0.912746, 0.934845) 0.983605 2.5 0.840000 0.936421 ( 0.925863, 0.946229) 0.987581 2.6 0.852071 0.945504 ( 0.935649, 0.954593) 0.990678 2.7 0.862826 0.955041 ( 0.946004, 0.963295) 0.993066 2.8 0.872449 0.958220 ( 0.949478, 0.966173) 0.994890 2.9 0.881094 0.964578 ( 0.956468, 0.971889) 0.996268 3.0 0.888889 0.970936 ( 0.963525, 0.977536) 0.997300 3.1 0.895942 0.976839 ( 0.970159, 0.982700) 0.998065 3.2 0.902344 0.980018 ( 0.973774, 0.985438) 0.998626 3.3 0.908173 0.984105 ( 0.978480, 0.988899) 0.999033 3.4 0.913495 0.985014 ( 0.979537, 0.989657) 0.999326 3.5 0.918367 0.989555 ( 0.984906, 0.993365) 0.999535 3.6 0.922840 0.991826 ( 0.987662, 0.995146) 0.999682 3.7 0.926954 0.993188 ( 0.989351, 0.996181) 0.999784 3.8 0.930748 0.994550 ( 0.991075, 0.997180) 0.999855 3.9 0.934254 0.998183 ( 0.996022, 0.999505) 0.999904 4.0 0.937500 0.999092 ( 0.997471, 0.999890) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 3.9993 0.0009 0.0518 0.0518 2 5.1560 0.0054 0.0675 0.0673 3 7.0740 0.0133 0.0904 0.0894 4 9.0788 0.0416 0.1169 0.1093 5 9.8080 0.0778 0.1620 0.1421 6 9.4829 0.0613 0.1647 0.1529 7 8.5010 0.0337 0.1669 0.1634 8 7.1262 0.0147 0.1649 0.1643 9 5.4001 0.0029 0.1686 0.1686 10 4.7627 0.0023 0.1746 0.1746 Last line is the total ========== Pairwise BAR ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.051317 ( 0.042496, 0.060909) 0.079656 0.2 -24.000000 0.112171 ( 0.099331, 0.125678) 0.158519 0.3 -10.111111 0.176203 ( 0.160576, 0.192388) 0.235823 0.4 -5.250000 0.227975 ( 0.210693, 0.245724) 0.310843 0.5 -3.000000 0.283833 ( 0.265194, 0.302843) 0.382925 0.6 -1.777778 0.331063 ( 0.311559, 0.350857) 0.451494 0.7 -1.040816 0.391462 ( 0.371177, 0.411935) 0.516073 0.8 -0.562500 0.444142 ( 0.423443, 0.464936) 0.576289 0.9 -0.234568 0.483197 ( 0.462346, 0.504077) 0.631880 1.0 -0.000000 0.537239 ( 0.516388, 0.558026) 0.682689 1.1 0.173554 0.581744 ( 0.561077, 0.602270) 0.728668 1.2 0.305556 0.619437 ( 0.599062, 0.639607) 0.769861 1.3 0.408284 0.654859 ( 0.634876, 0.674576) 0.806399 1.4 0.489796 0.691190 ( 0.671735, 0.710315) 0.838487 1.5 0.555556 0.720708 ( 0.701786, 0.739251) 0.866386 1.6 0.609375 0.749319 ( 0.731009, 0.767200) 0.890401 1.7 0.653979 0.787466 ( 0.770138, 0.804299) 0.910869 1.8 0.691358 0.816076 ( 0.799630, 0.831979) 0.928139 1.9 0.722992 0.839237 ( 0.823611, 0.854280) 0.942567 2.0 0.750000 0.858311 ( 0.843444, 0.872561) 0.954500 2.1 0.773243 0.876930 ( 0.862892, 0.890320) 0.964271 2.2 0.793388 0.893279 ( 0.880052, 0.905829) 0.972193 2.3 0.810964 0.908265 ( 0.895866, 0.919963) 0.978552 2.4 0.826389 0.920527 ( 0.908876, 0.931454) 0.983605 2.5 0.840000 0.932334 ( 0.921480, 0.942445) 0.987581 2.6 0.852071 0.941871 ( 0.931727, 0.951255) 0.990678 2.7 0.862826 0.950045 ( 0.940568, 0.958748) 0.993066 2.8 0.872449 0.956403 ( 0.947492, 0.964530) 0.994890 2.9 0.881094 0.961853 ( 0.953465, 0.969447) 0.996268 3.0 0.888889 0.965486 ( 0.957472, 0.972700) 0.997300 3.1 0.895942 0.971390 ( 0.964033, 0.977936) 0.998065 3.2 0.902344 0.975477 ( 0.968620, 0.981517) 0.998626 3.3 0.908173 0.981381 ( 0.975334, 0.986600) 0.999033 3.4 0.913495 0.983651 ( 0.977953, 0.988519) 0.999326 3.5 0.918367 0.986376 ( 0.981132, 0.990785) 0.999535 3.6 0.922840 0.989101 ( 0.984361, 0.993001) 0.999682 3.7 0.926954 0.990917 ( 0.986552, 0.994441) 0.999784 3.8 0.930748 0.993642 ( 0.989921, 0.996518) 0.999855 3.9 0.934254 0.994550 ( 0.991075, 0.997180) 0.999904 4.0 0.937500 0.996821 ( 0.994076, 0.998720) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 3.9988 0.0005 0.0511 0.0511 2 5.1554 0.0047 0.0666 0.0664 3 7.0734 0.0127 0.0895 0.0886 4 9.0800 0.0427 0.1176 0.1096 5 9.8080 0.0777 0.1625 0.1427 6 9.4826 0.0610 0.1649 0.1532 7 8.5017 0.0345 0.1674 0.1638 8 7.1276 0.0161 0.1656 0.1648 9 5.4013 0.0042 0.1686 0.1686 10 4.7639 0.0035 0.1747 0.1747 Last line is the total ========== MBAR ========== The uncertainty estimates are tested in this section. If the error is normally distributed, the actual error will be less than a multiplier 'alpha' times the computed uncertainty 'sigma' a fraction of time given by: P(error < alpha sigma) = erf(alpha / sqrt(2)) For example, the true error should be less than 1.0 * sigma (one standard deviation) a total of 68% of the time, and less than 2.0 * sigma (two standard deviations) 95% of the time. The observed fraction of the time that error < alpha sigma, and its uncertainty, is given as 'obs' (with uncertainty 'obs err') below. This should be compared to the column labeled 'normal'. A weak lower bound that holds regardless of how the error is distributed is given by Chebyshev's inequality, and is listed as 'cheby' below. Uncertainty estimates are tested for both free energy differences and expectations. Error vs. alpha for free energies alpha cheby obs obs err normal 0.1 -99.000000 0.064941 ( 0.055031, 0.075599) 0.079656 0.2 -24.000000 0.133969 ( 0.120064, 0.148504) 0.158519 0.3 -10.111111 0.202089 ( 0.185580, 0.219111) 0.235823 0.4 -5.250000 0.259764 ( 0.241662, 0.278279) 0.310843 0.5 -3.000000 0.319255 ( 0.299946, 0.338876) 0.382925 0.6 -1.777778 0.383288 ( 0.363088, 0.403688) 0.451494 0.7 -1.040816 0.455041 ( 0.434287, 0.475872) 0.516073 0.8 -0.562500 0.510445 ( 0.489564, 0.531309) 0.576289 0.9 -0.234568 0.569028 ( 0.548292, 0.589646) 0.631880 1.0 -0.000000 0.621708 ( 0.601354, 0.641852) 0.682689 1.1 0.173554 0.666213 ( 0.646380, 0.685759) 0.728668 1.2 0.305556 0.702089 ( 0.682820, 0.721010) 0.769861 1.3 0.408284 0.742053 ( 0.723578, 0.760111) 0.806399 1.4 0.489796 0.768392 ( 0.750548, 0.785775) 0.838487 1.5 0.555556 0.800636 ( 0.783697, 0.817057) 0.866386 1.6 0.609375 0.827884 ( 0.811842, 0.843361) 0.890401 1.7 0.653979 0.854678 ( 0.839660, 0.869085) 0.910869 1.8 0.691358 0.875114 ( 0.860990, 0.888592) 0.928139 1.9 0.722992 0.896004 ( 0.882921, 0.908405) 0.942567 2.0 0.750000 0.914169 ( 0.902121, 0.925505) 0.954500 2.1 0.773243 0.921435 ( 0.909843, 0.932303) 0.964271 2.2 0.793388 0.933697 ( 0.922940, 0.943708) 0.972193 2.3 0.810964 0.945050 ( 0.935158, 0.954177) 0.978552 2.4 0.826389 0.954587 ( 0.945509, 0.962883) 0.983605 2.5 0.840000 0.965032 ( 0.956970, 0.972294) 0.987581 2.6 0.852071 0.970027 ( 0.962512, 0.976734) 0.990678 2.7 0.862826 0.973660 ( 0.966576, 0.979931) 0.993066 2.8 0.872449 0.975023 ( 0.968108, 0.981121) 0.994890 2.9 0.881094 0.978656 ( 0.972220, 0.984269) 0.996268 3.0 0.888889 0.983197 ( 0.977427, 0.988137) 0.997300 3.1 0.895942 0.987284 ( 0.982202, 0.991530) 0.998065 3.2 0.902344 0.992280 ( 0.988222, 0.995494) 0.998626 3.3 0.908173 0.995005 ( 0.991660, 0.997503) 0.999033 3.4 0.913495 0.998183 ( 0.996022, 0.999505) 0.999326 3.5 0.918367 0.999092 ( 0.997471, 0.999890) 0.999535 3.6 0.922840 0.999092 ( 0.997471, 0.999890) 0.999682 3.7 0.926954 0.999546 ( 0.998325, 0.999988) 0.999784 3.8 0.930748 0.999546 ( 0.998325, 0.999988) 0.999855 3.9 0.934254 0.999546 ( 0.998325, 0.999988) 0.999904 4.0 0.937500 0.999546 ( 0.998325, 0.999988) 0.999937 i average bias rms_error stddev ----------------------------------------------------- 0 0.0000 0.0000 0.0000 0.0000 1 4.0001 0.0017 0.0537 0.0537 2 5.1549 0.0043 0.0676 0.0675 3 7.0713 0.0105 0.0880 0.0873 4 9.0755 0.0382 0.1099 0.1031 5 9.8033 0.0731 0.1518 0.1330 6 9.4768 0.0552 0.1529 0.1426 7 8.4966 0.0294 0.1585 0.1557 8 7.1225 0.0109 0.1603 0.1599 9 5.3973 0.0002 0.1643 0.1643 10 4.7600 -0.0004 0.1694 0.1694 Last line is the total