Exploring protein flexibility: incorporating structural ensembles from crystal structures and simulation into virtual screening protocols.

ABSTRACT: The capacity of proteins to adapt their structure in response to various perturbations including covalent modifications, and interactions with ligands and other proteins plays a key role in biological processes. Here, we explore the ability of molecular dynamics (MD), replica exchange molecular dynamics (REMD), and a library of structures of crystal-ligand complexes, to sample the protein conformational landscape and especially the accessible ligand binding site geometry. The extent of conformational space sampled is measured by the diversity of the shapes of the ligand binding sites. Since our focus here is the effect of this plasticity on the ability to identify active compounds through virtual screening, we use the structures generated by these techniques to generate a small ensemble fo

SUBMITTER: Osguthorpe DJ 

PROVIDER: S-EPMC3376248 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature