Molecular Simulation Trajectories Archive

Data Source:

All currently available trajectories were generated by members of the Pande Lab.

The work is described in detail in the following reference:

Ensign DL, Kasson PM, Pande VS. "Heterogeneity even at the speed limit of folding: large-scale molecular dynamics study of a fast-folding variant of the villin headpiece" J. Mol. Biol. (2007) 374 (3): 806-816.PUBMED.

The above paper describes the first set of results generated using the Symmetric Multi-processing (SMP) clients. The main advantage of using SMP for these sorts of calculations is that the amount of computation that one client can do is several times larger than the traditional clients. This means that our simulations can get many times longer than before; in fact, this has allowed us to generate several hundred folding trajectories of the fastest-folding protein known, the HP35-NleNle variant of the villin headpiece subdomain. In this paper, because our simulation time scales compare well to the 700-nanosecond experimental folding time of this protein, AND we've generated enough trajectories to get good statistics, we can shed some light on the experimental results. To summarize the results, the first helix of the protein was thought to be highly structured in the unfolded state of the protein; we've suggested that structure in this part of the molecule is not enough to lead to fast folding, and that time scales longer than the 700-ns mark may be present in this system.

ABSTRACT: We have performed molecular dynamics simulations on a set of nine unfolded conformations of the fastest-folding protein yet discovered, a variant of the villin headpiece subdomain (HP-35 NleNle). The simulations were generated using a new distributed computing method, yielding hundreds of trajectories each on a time scale comparable to the experimental folding time, despite the large (10,000 atom) size of the simulation system. This strategy eliminates the need to assume a two-state kinetic model or to build a Markov state model. The relaxation to the folded state at 300 K from the unfolded configurations (generated by simulation at 373 K) was monitored by a method intended to reflect the experimental observable (quenching of tryptophan by histidine). We also monitored the relaxation to the native state by directly comparing structural snapshots with the native state. The rate of relaxation to the native state and the number of resolvable kinetic time scales both depend upon starting structure. Moreover, starting structures with folding rates most similar to experiment show some native-like structure in the N-terminal helix (helix 1) and the phenylalanine residues constituting the hydrophobic core, suggesting that these elements may exist in the experimentally relevant unfolded state. Our large-scale simulation data reveal kinetic complexity not resolved in the experimental data. Based on these findings, we propose additional experiments to further probe the kinetics of villin folding.

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