Rapid Rescoring and Refinement of Ligand-Receptor Complexes Using Replica Exchange Molecular Dynamics with a Monte Carlo Pose Reservoir.

ABSTRACT: Virtual screening (VS) involves generation of poses for a library of ligands and ranking using simplified energy functions and limited flexibility. Top-scored poses are used to rank and prioritize ligands. Here, we adapt the reservoir replica exchange molecular dynamics (res-REMD) method to rerank poses generated through VS. REMD simulations are carried out but with occasional Monte Carlo jumps to alternate VS-generated poses using a Metropolis criterion. The simulations converge within 10 ns for all systems, generating populations of alternate poses in the context of fully flexible ligand and protein side chains. The protocol is applied to four model protein-ligand complexes, where DOCK resulted in two successes and two scoring failures. In all four systems, the most populated cluster fro

SUBMITTER: Alcantara J 

PROVIDER: S-EPMC10702174 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature