title: Use of the X-ray structure of the Beta2-adrenergic receptor for drug discovery.
abstract: The recently reported X-ray structure of the Beta2-adrenergic receptor, the first reported crystal structure of a ligand-mediated GPCR, is used to explore its utility in computer-aided drug design. Validations were conducted with known beta blockers. This was followed by high-throughput docking studies with proprietary and commercial databases to further validate the X-ray structure's usefulness as a design tool and to explore the potential for discovery of novel chemical classes acting as Beta2 inhibitors. Our results include the finding of ligands with traditional beta-blocker motifs as well as new motifs, thereby serving to both validate the approach and project its usefulness in the finding and design of novel compounds.
authors.affiliation: Department of Computational Chemistry, Lundbeck Research USA, 215 College Road, Paramus, NJ 07652-1431, USA. swt@lundbeck.com
authors.forename: Sid
authors.initials: S
authors.lastname: Topiol
authors.forename: Michael
authors.initials: M
authors.lastname: Sabio
mesh_terms: D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2