Probing protein stability: towards a computational atomistic, reliable, affordable, and improvable model.

ABSTRACT: We present an improved application of a recently proposed computational method designed to evaluate the change of free energy as a function of the average value of a suitably chosen collective variable in proteins. The method is based on a full atomistic description of the protein and its environment. The goal is to understand how the protein melting temperature changes upon single-point mutations, because the sign of the temperature variation will allow us to discriminate stabilizing vs. destabilizing mutations in protein sequences. In this refined application the method is based on altruistic well-tempered metadynamics, a variant of multiple-walkers metadynamics. The resulting metastatistics is then modulated by the maximal constrained entropy principle. The latter turns out to be especi

SUBMITTER: Nobili G 

PROVIDER: S-EPMC10267363 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature