Evidence of conformational selection driving the formation of ligand binding sites in protein-protein interfaces.

ABSTRACT: Many protein-protein interactions (PPIs) are compelling targets for drug discovery, and in a number of cases can be disrupted by small molecules. The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-free and ligand-bound structures. To avoid any potential bias, we focus on ensembles of ligand-free protein conformations obtained by nuclear magnetic resonance (NMR) techniques and deposited in the Protein Data Bank, rather than on ensembles specifically generated for this study. The measures used for structure comparison are based on detecting binding hot spots, i.e., protein regions that are major contributors to the binding free energy. The main tool of the analysis is computational sol

SUBMITTER: Bohnuud T 

PROVIDER: S-EPMC4183424 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature