Extended-ensemble docking to probe dynamic variation of ligand binding sites during large-scale structural changes of proteins.

ABSTRACT: Proteins can sample a broad landscape as they undergo conformational transition between different functional states. At the same time, as key players in almost all cellular processes, proteins are important drug targets. Considering the different conformational states of a protein is therefore central for a successful drug-design strategy. Here we introduce a novel docking protocol, termed extended-ensemble docking, pertaining to proteins that undergo large-scale (global) conformational changes during their function. In its application to multidrug ABC-transporter P-glycoprotein (Pgp), extensive non-equilibrium molecular dynamics simulations employing system-specific collective variables are first used to describe the transition cycle of the transporter. An extended set of conformations (e

SUBMITTER: Kapoor K 

PROVIDER: S-EPMC8985516 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature