Use of the X-ray structure of the Beta2-adrenergic receptor for drug discovery

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.

Graphical abstractWe explore the utility of the Beta2-adrenergic receptor’s X-ray structure in drug design including high-throughput docking. Results validate the approach and project its usefulness in finding and designing novel compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide