Molecular docking screening using agonist-bound GPCR structures: probing the A2A adenosine receptor.

ABSTRACT: Crystal structures of G protein-coupled receptors (GPCRs) have recently revealed the molecular basis of ligand binding and activation, which has provided exciting opportunities for structure-based drug design. The A2A adenosine receptor (A2AAR) is a promising therapeutic target for cardiovascular diseases, but progress in this area is limited by the lack of novel agonist scaffolds. We carried out docking screens of 6.7 million commercially available molecules against active-like conformations of the A2AAR to investigate whether these structures could guide the discovery of agonists. Nine out of the 20 predicted agonists were confirmed to be A2AAR ligands, but none of these activated the ARs. The difficulties in discovering AR agonists using structure-based methods originated from limited a

SUBMITTER: Rodriguez D 

PROVIDER: S-EPMC4474233 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature