title: Computational modeling study of functional microdomains in cannabinoid receptor type 1.
abstract: The seven transmembrane helices (TMH) G-protein-coupled receptors (GPCRs) constitute one of the largest superfamily of signaling proteins found in mammals. Some of its members, in which the cannabinoid (CB) receptors are included, stand out because their functional states can be modulated by a broad spectrum of effector molecules. The relative ligand promiscuity exhibited by these receptors could be related with particular attributes conferred by their molecular architecture and represents a motivating issue to be explored. In this regard, this study represents an effort to investigate the cannabinoid receptor type 1 (CB1) ligand recognition plasticity, using comparative modeling, molecular dynamics (MD) simulations and docking. Our results suggest that a cooperative set of subtle structural rearrangements within the TMHs provide to the CB1 protein the plasticity to reach alternate configurations. These changes include the relaxation of intramolecular constraints, the rotations, translations and kinks of the majority of TMHs and the reorganization of the ligand binding cavities.
authors.affiliation: Centre for Bioinformatics CBUC, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Portugal 49-6513492, Santiago, Chile. angel@cbuc.cl
authors.forename: Angel
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Leonardo Sepulveda
authors.initials: LS
authors.lastname: Duran
authors.forename: Raul
authors.initials: R
authors.lastname: Araya-Secchi
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garate
authors.forename: C David
authors.initials: CD
authors.lastname: Pessoa-Mahana
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lagos
authors.forename: Tomas
authors.initials: T
authors.lastname: Perez-Acle
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D003198:Computer Simulation; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry*
chemical_list: D008024:Ligands; D043884:Receptor, Cannabinoid, CB1