Robust Prediction of Relative Binding Energies for Protein-Protein Complex Mutations Using Free Energy Perturbation Calculations.

ABSTRACT: Computational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such methods must reach a high level of reliability, accuracy, and automation to be effectively deployed in practical industrial settings in a way that impacts protein design projects. Here, we present a benchmark study for the calculation of relative changes in protein-protein binding affinity for single point mutations across a variety of systems from the literature, using free energy perturbation (FEP+) calculations. We describe a method for robust treatment of alternate protonation states for titratable amino acids, which yields improved correlation with and reduced error compared to experimental binding free energies. Following careful analysis o

SUBMITTER: Sampson JM 

PROVIDER: S-EPMC11339910 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature