A strategy for proline and glycine mutations to proteins with alchemical free energy calculations.

ABSTRACT: Computation of the thermodynamic consequences of protein mutations holds great promise in protein biophysics and design. Alchemical free energy methods can give improved estimates of mutational free energies, and are already widely used in calculations of relative and absolute binding free energies in small molecule design problems. In principle, alchemical methods can address any amino acid mutation with an appropriate alchemical pathway, but identifying a strategy that produces such a path for proline and glycine mutations is an ongoing challenge. Most current strategies perturb only side chain atoms, while proline and glycine mutations also alter the backbone parameters and backbone ring topology. Some strategies also perturb backbone parameters and enable glycine mutations. This work p

SUBMITTER: Hayes RL 

PROVIDER: S-EPMC8628859 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature