Performance of virtual screening against GPCR homology models: Impact of template selection and treatment of binding site plasticity.

ABSTRACT: Rational drug design for G protein-coupled receptors (GPCRs) is limited by the small number of available atomic resolution structures. We assessed the use of homology modeling to predict the structures of two therapeutically relevant GPCRs and strategies to improve the performance of virtual screening against modeled binding sites. Homology models of the D2 dopamine (D2R) and serotonin 5-HT2A receptors (5-HT2AR) were generated based on crystal structures of 16 different GPCRs. Comparison of the homology models to D2R and 5-HT2AR crystal structures showed that accurate predictions could be obtained, but not necessarily using the most closely related template. Assessment of virtual screening performance was based on molecular docking of ligands and decoys. The results demonstrated that sever

SUBMITTER: Jaiteh M 

PROVIDER: S-EPMC7135368 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature