Improving virtual screening of G protein-coupled receptors via ligand-directed modeling.

ABSTRACT: G protein-coupled receptors (GPCRs) play crucial roles in cell physiology and pathophysiology. There is increasing interest in using structural information for virtual screening (VS) of libraries and for structure-based drug design to identify novel agonist or antagonist leads. However, the sparse availability of experimentally determined GPCR/ligand complex structures with diverse ligands impedes the application of structure-based drug design (SBDD) programs directed to identifying new molecules with a select pharmacology. In this study, we apply ligand-directed modeling (LDM) to available GPCR X-ray structures to improve VS performance and selectivity towards molecules of specific pharmacological profile. The described method refines a GPCR binding pocket conformation using a single know

SUBMITTER: Coudrat T 

PROVIDER: S-EPMC5708846 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature