title: Application of Monte Carlo-based receptor ensemble docking to virtual screening for GPCR ligands.
abstract: Receptor ensemble docking (RED) is an effective strategy to account for receptor flexibility in the course of a docking-based virtual screening campaign. Such an approach can be applied when multiple crystal structures of a receptor have been solved, but it can also be applied when only a single crystal structure is available. In this case, alternative structures can be generated from the latter by computational means and subsequently applied to RED. Here, we illustrate how such conformers can be generated by subjecting a crystal structure to Monte Carlo conformational searches. Through a controlled virtual screening experiment, we then show the applicability of such a strategy to the identification of ligands of the β(2) adrenergic receptor, a G protein-coupled receptor activated by epinephrine. Requiring the availability of one crystal structure only, this strategy is applicable to all systems for which multiple experimentally elucidated structures are not available.
authors: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago the Compostela, Spain.
authors: Santiago
authors: S
authors: Vilar
authors: Stefano
authors: S
authors: Costanzi
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004837:Epinephrine / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation / Q000379:methods* / Q000706:statistics & numerical data; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D018343:Receptors, Adrenergic, beta-2; D004837:Epinephrine