title: Distinct interactions between the human adrenergic beta(2) receptor and Galpha(s)--an in silico study.
abstract: The aim of this study was to perform an in silico analysis of the interaction of the human beta(2) adrenergic receptor with Galpha(s). In a first step, a systematic surface-interaction-scan between the inactive or active human beta(2) adrenergic receptor and Galpha(s) was performed in order to gain knowledge about energetically preferred areas on the potential energy surface. Subsequently, two energetically favored regions for the active human beta(2) adrenergic receptor-Galpha(s) complex were identified. Two representative complex structures were put into a POPC (1-palmitoyl-2-oleoyl-phosphatidylcholine) bilayer and solvated in order to perform molecular dynamic simulations. The simulations revealed that both conformations, which have comparable potential energy, are stable. A mean number of about 14 hydrogen bonds was observed between the active receptor and Galpha(s) for both conformations. Based on these results, two energetically favored beta(2)-Galpha(s)complexes can be proposed.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Chemistry and Pharmacy, University of Regensburg, Universitätsstrasse 31, Regensburg, Germany. andrea.strasser@chemie.uni-regensburg.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Strasser
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wittmann
mesh_terms: D000595:Amino Acid Sequence; D002864:Chromogranins; D019295:Computational Biology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: C553443:ADRB2 protein, human; D002864:Chromogranins; D018343:Receptors, Adrenergic, beta-2; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs