Accelerated flexible protein-ligand docking using Hamiltonian replica exchange with a repulsive biasing potential.

ABSTRACT: A molecular dynamics replica exchange based method has been developed that allows rapid identification of putative ligand binding sites on the surface of biomolecules. The approach employs a set of ambiguity restraints in replica simulations between receptor and ligand that allow close contacts in the reference replica but promotes transient dissociation in higher replicas. This avoids long-lived trapping of the ligand or partner proteins at nonspecific, sticky, sites on the receptor molecule and results in accelerated exploration of the possible binding regions. In contrast to common docking methods that require knowledge of the binding site, exclude solvent and often keep parts of receptor and ligand rigid the approach allows for full flexibility of binding partners. Application to pepti

SUBMITTER: Ostermeir K 

PROVIDER: S-EPMC5313199 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature