MnM-W-MMGBSA: A Computational Strategy to Improve Relative Binding Free Energies of Protein-Protein Interaction Systems.

ABSTRACT: Protein-protein interactions (PPIs) have become increasingly attractive as therapeutic targets due to their central role in regulating cellular functions. Despite computational advancements, accurately estimating binding free energies for PPIs remains challenging due to the dynamic and critically solvent-exposed nature of their interfaces. In this study, we present MnM-W-MMGBSA (i.e., MM-GBSA with Mix-and-Match sampling and water inclusion), a method that addresses these challenges by incorporating both conformational flexibility and interfacial solvation effects. We thoroughly demonstrated the applicability of MnM-W-MMGBSA across a diverse set of 20 PPI systems and validated its robustness using two distinct and rigorous simulation schemes. We demonstrate that our protocol improves correl

SUBMITTER: Hasan MN 

PROVIDER: S-EPMC12703734 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature