Critical analysis of the successes and failures of homology models of G protein-coupled receptors.

ABSTRACT: We present a critical assessment of the performance of our homology model refinement method for G protein-coupled receptors (GPCRs), called LITICon that led to top ranking structures in a recent structure prediction assessment GPCRDOCK2010. GPCRs form the largest class of drug targets for which only a few crystal structures are currently available. Therefore, accurate homology models are essential for drug design in these receptors. We submitted five models each for human chemokine CXCR4 (bound to small molecule IT1t and peptide CVX15) and dopamine D3DR (bound to small molecule eticlopride) before the crystal structures were published. Our models in both CXCR4/IT1t and D3/eticlopride assessments were ranked first and second, respectively, by ligand RMSD to the crystal structures. For both

SUBMITTER: Bhattacharya S 

PROVIDER: S-EPMC3785289 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature