Long Time Scale Ensemble Methods in Molecular Dynamics: Ligand-Protein Interactions and Allostery in SARS-CoV-2 Targets.

ABSTRACT: We subject a series of five protein-ligand systems which contain important SARS-CoV-2 targets, 3-chymotrypsin-like protease (3CLPro), papain-like protease, and adenosine ribose phosphatase, to long time scale and adaptive sampling molecular dynamics simulations. By performing ensembles of ten or twelve 10 μs simulations for each system, we accurately and reproducibly determine ligand binding sites, both crystallographically resolved and otherwise, thereby discovering binding sites that can be exploited for drug discovery. We also report robust, ensemble-based observation of conformational changes that occur at the main binding site of 3CLPro due to the presence of another ligand at an allosteric binding site explaining the underlying cascade of events responsible for its inhibitory effect.

SUBMITTER: Bhati AP 

PROVIDER: S-EPMC10241325 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature