title: Prediction of structure of G-protein coupled receptors and of bound ligands, with applications for drug design.
abstract: G protein-coupled receptors (GPCRs) mediate the senses of vision, smell, taste, and pain. They are also involved in cell recognition and communication processes, making them a prominent superfamily for drug targets. Unfortunately, the atomic-level structure is available from experiment only for bovine rhodopsin. We report here improvements in methods (MembStruk and HierDock) for predicting the structures of GPCRs, including bound ligands, with applications to prostanoid and Urotensin GPCRs. We find that the predicted binding sites are consistent with available mutation and SAR data, suggesting that the predicted structures are sufficiently accurate for drug design applications.
authors.affiliation: Materials and Process Simulation Center (MC 139-74), California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Li
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011453:Prostaglandins / Q000378:metabolism; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014579:Urotensins / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D011453:Prostaglandins; D043562:Receptors, G-Protein-Coupled; D011982:Receptors, Prostaglandin; C121697:UTS2R protein, human; D014579:Urotensins