G protein-coupled receptors (GPCRs) are a large family of integral transmembrane proteins involved in cell signaling and are the targets of many drugs. Wallace Chan and his graduate mentor Yang Zhang developed a virtual-screening pipeline called MAGELLAN (Michigan G protein-coupled Receptor Ligand-Based Virtual Screen) to find molecules that are predicted to bind to specific GPCRs. MAGELLAN 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 virtual screening. Their paper describes development and testing of the pipeline and shows that it compares favorably with other cutting-edge docking- and ligand-based methods for virtual screening. Wallace is currently a postdoctoral fellow in the Pharmacology Department at the University of Michigan Medical School.
The MAGELLAN webserver, together with the virtual screening results for various human GPCRs and the filtered ligand sets, are available and downloadable HERE.
Read the JMB paper HERE.