title: Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor.
abstract: The recently solved high-resolution X-ray structure of the beta2 adrenergic receptor has been challenged for its ability to discriminate inverse agonists/antagonists from partial/full agonists. Whereas the X-ray structure of the ground state receptor was unsuitable to distinguish true ligands with different functional effects, modifying this structure to reflect early conformational events in receptor activation led to a receptor model able to selectively retrieve full and partial agonists by structure-based virtual screening. The use of a topological scoring function based on molecular interaction fingerprints was shown to be mandatory to properly rank docking poses and achieve acceptable enrichments for partial and full agonists only.
authors.affiliation: Bioinformatics of the Drug, Institut Gilbert Laustriat, CNRS UMR 7175-LC1, Université Louis Pasteur Strasbourg, 74 Route du Rhin, 67401 Illkirch, France.
authors.forename: Chris
authors.initials: C
authors.lastname: de Graaf
authors.forename: Didier
authors.initials: D
authors.lastname: Rognan
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007545:Isoproterenol / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D011412:Propanolamines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D008024:Ligands; D011412:Propanolamines; C014382:carazolol; D007545:Isoproterenol