Quantitative Characterization of the Impact of Protein-Protein Interactions on Ligand-Protein Binding: A Multi-Chain Dynamics Perturbation Analysis Method.

ABSTRACT: Many protein-protein interactions (PPIs) affect the ways in which small molecules bind to their constituent proteins, which can impact drug efficacy and regulatory mechanisms. While recent advances have improved our ability to independently predict both PPIs and ligand-protein interactions (LPIs), a comprehensive understanding of how PPIs affect LPIs is still lacking. Here, we examined 63 pairs of ligand-protein complexes in a benchmark dataset for protein-protein docking studies and quantified six typical effects of PPIs on LPIs. A multi-chain dynamics perturbation analysis method, called mcDPA, was developed to model these effects and used to predict small-molecule binding regions in protein-protein complexes. Our results illustrated that the mcDPA can capture the impact of

SUBMITTER: Li L 

PROVIDER: S-EPMC11394879 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature