title: Simulations of a G protein-coupled receptor homology model predict dynamic features and a ligand binding site.
abstract: A computational approach to predict structures of rhodopsin-like G protein-coupled receptors (GPCRs) is presented and evaluated by comparison to the X-ray structural models. By combining sequence alignment, the rhodopsin crystal structure, and point mutation data on the beta2 adrenoreceptor (b2ar), we predict a (-)-epinephrine-bound computational model of the beta2 adrenoreceptor. The model is evaluated by molecular dynamics simulations and by comparison with the recent X-ray structures of b2ar. The overall correspondence between the predicted and the X-ray structural model is high. Especially the prediction of the ligand binding site is accurate. This shows that the proposed dynamic homology modelling approach can be used to create reasonable models for the understanding of structure and dynamics of other rhodopsin-like GPCRs.
authors.affiliation: Department of Biophysics, University of Bochum, ND 04 North, 44780 Bochum, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wolf
authors.forename: Marcus
authors.initials: M
authors.lastname: Böckmann
authors.forename: Udo
authors.initials: U
authors.lastname: Höweler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schlitter
authors.forename: Klaus
authors.initials: K
authors.lastname: Gerwert
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004837:Epinephrine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D017354:Point Mutation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D018343:Receptors, Adrenergic, beta-2; D012243:Rhodopsin; D004837:Epinephrine