Virtual Screening of Human Class-A GPCRs Using Ligand Profiles Built on Multiple Ligand-Receptor Interactions.

ABSTRACT: G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins responsible for cellular signal transductions. Identification of therapeutic compounds to regulate physiological processes is an important first step of drug discovery. We proposed MAGELLAN, a novel hierarchical virtual-screening (VS) pipeline, which starts with low-resolution protein structure prediction and structure-based binding-site identification, followed by homologous GPCR detections through structure and orthosteric binding-site comparisons. Ligand profiles constructed from the homologous ligand-GPCR complexes are then used to thread through compound databases for VS. The pipeline was first tested in a large-scale retrospective screening experiment against 224 human Class A GPCRs, where MAGELLAN a

SUBMITTER: Chan WKB 

PROVIDER: S-EPMC7415681 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature