Relative Binding Affinity Prediction of Charge-Changing Sequence Mutations with FEP in Protein-Protein Interfaces.

ABSTRACT: Building on the substantial progress that has been made in using free energy perturbation (FEP) methods to predict the relative binding affinities of small molecule ligands to proteins, we have previously shown that results of similar quality can be obtained in predicting the effect of mutations on the binding affinity of protein-protein complexes. However, these results were restricted to mutations which did not change the net charge of the side chains due to known difficulties with modeling perturbations involving a change in charge in FEP. Various methods have been proposed to address this problem. Here we apply the co-alchemical water approach to study the efficacy of FEP calculations of charge changing mutations at the protein-protein interface for the antibody-gp120 system investigat

SUBMITTER: Clark AJ 

PROVIDER: S-EPMC6453258 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature