Looking for critical opinion on MD simulations
Hi all,
I am currently designing de novo proteins based on a wild type. I want to use MD to check if the mutations I am adding are likely to have destabilised the protein. This is so I can have a rationale for reducing my design space, and prioritise variants to express at scale.
My proteins are approx 97 amino acids long.
I am currently in a production run cycle - my plan is to run 5 x 200ns simulations for each protein variant and compare RMSD, Rg, RMSF, and hydrogen bond number throughout the run to infer improved or reduced stability. RMSF for functional regions specifically I.e. what do the variations do to rigidity of the scaffold and the functional region.
I have expressed the proteins and will be experimentally validating the runs by testing thermostability and activity of the proteins in vitro.
For people who are fluent in MD - does this sound like something that would hold up and be defensible?
Thanks for your help!