Enhancing Side Chain Rotamer Sampling Using Nonequilibrium Candidate Monte Carlo.

ABSTRACT: Molecular simulations are a valuable tool for studying biomolecular motions and thermodynamics. However, such motions can be slow compared to simulation time scales, yet critical. Specifically, adequate sampling of side chain motions in protein binding pockets is crucial for obtaining accurate estimates of ligand binding free energies from molecular simulations. The time scale of side chain rotamer flips can range from a few ps to several hundred ns or longer, particularly in crowded environments like the interior of proteins. Here, we apply a mixed nonequilibrium candidate Monte Carlo (NCMC)/molecular dynamics (MD) method to enhance sampling of side chain rotamers. The NCMC portion of our method applies a switching protocol wherein the steric and electrostatic interactions between target

SUBMITTER: Burley KH 

PROVIDER: S-EPMC6537864 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature