Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics.

ABSTRACT: We present a method to identify small molecule ligand binding sites and poses within a given protein crystal structure using GPU-accelerated Hamiltonian replica exchange molecular dynamics simulations. The Hamiltonians used vary from the physical end state of protein interacting with the ligand to an unphysical end state where the ligand does not interact with the protein. As replicas explore the space of Hamiltonians interpolating between these states, the ligand can rapidly escape local minima and explore potential binding sites. Geometric restraints keep the ligands from leaving the vicinity of the protein and an alchemical pathway designed to increase phase space overlap between intermediates ensures good mixing. Because of the rigorous statistical mechanical nature of the Hamiltonian

SUBMITTER: Wang K 

PROVIDER: S-EPMC4154199 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature