GPCR 3D homology models for ligand screening: lessons learned from blind predictions of adenosine A2a receptor complex.

ABSTRACT: Proteins of the G-protein coupled receptor (GPCR) family present numerous attractive targets for rational drug design, but also a formidable challenge for identification and conformational modeling of their 3D structure. A recently performed assessment of blind predictions of adenosine A2a receptor (AA2AR) structure in complex with ZM241385 (ZMA) antagonist provided a first example of unbiased evaluation of the current modeling algorithms on a GPCR target with approximately 30% sequence identity to the closest structural template. Several of the 29 groups participating in this assessment exercise (Michino et al., doi: 10.1038/nrd2877) successfully predicted the overall position of the ligand ZMA in the AA2AR ligand binding pocket, however models from only three groups captured more than 40

SUBMITTER: Katritch V 

PROVIDER: S-EPMC2805832 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature