Docking-based virtual screening for ligands of G protein-coupled receptors: not only crystal structures but also in silico models.

ABSTRACT: G protein-coupled receptors (GPCRs) regulate a wide range of physiological functions and hold great pharmaceutical interest. Using the β(2)-adrenergic receptor as a case study, this article explores the applicability of docking-based virtual screening to the discovery of GPCR ligands and defines methods intended to improve the screening performance. Our controlled computational experiments were performed on a compound dataset containing known agonists and blockers of the receptor as well as a large number of decoys. The screening based on the structure of the receptor crystallized in complex with its inverse agonist carazolol yielded excellent results, with a clearly delineated prioritization of ligands over decoys. Blockers generally were preferred over agonists; however, agonists were al

SUBMITTER: Vilar S 

PROVIDER: S-EPMC3035735 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature