How to introduce mutation/modification

[Pujan Ajmera]

Hi, I was wondering how I can mutate a protein residue within or outside of openmm, such that my files are compatible with it? From my trajectory, I yielded a pdb file, as well as an xml state file. I have a psf file with the rest of the parameter files as well from before. My system has too many atoms to be properly loaded by chimerax.

[Peter Eastman]

PDBFixer has an applyMutations() function that might be what you want.

[Pujan Ajmera]

To clarify then, how would I make sure the psf file is also properly modified? I imagine for example, a MET-->VAL mutation, there would be a significant connectivity change that needs to be specified

[Peter Eastman]

It doesn't. There are two possible workflows. One is to do your modelling in OpenMM, and then parameterize it with OpenMM. The other is to do your modelling with CHARMM, parameterize it with CHARMM, and then load the PSF file into OpenMM. OpenMM can't modify the structure loaded from the PSF while preserving the parameterization. If you think about it, you can see why that would have to be the case: it doesn't have parameters for the mutated residue.

So if you use PDBFixer to mutate the residue, you have to reparameterize the whole system from scratch with a ForceField.

[Pujan Ajmera]

Okay got it, I think then I will do the following (for other users that see this):

1) Get the crd file from the last frame in openmm (parmed can do this nicely)
2) Use charmm to mutate and regenerate psf and crd file, I found some builder scripts that can handle this
3) Reload those corresponding files into openmm

Thanks for your help!