title: The Role of Binding Kinetics in GPCR Drug Discovery.
abstract: Binding kinetics are the rates of association and dissociation of a drug-protein complex and are important molecular descriptors for the optimization of drug binding to G-protein coupled receptors (GPCRs). There are now many examples of binding kinetics in GPCR drug discovery. In this report, the first principles and examples of binding kinetics in GPCR drug discovery are reviewed. Addressed are the influence of binding kinetics on the translation of binding to the therapeutic window in the context of the equilibrium state of the system and molecular mechanisms of slow binding including induced fit, displacement of water, rebinding and heterovalency.
authors.forename: David C
authors.initials: DC
authors.lastname: Swinney
authors.forename: Brad A
authors.initials: BA
authors.lastname: Haubrich
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Liefde
authors.affiliation: Institute for Rare and Neglected Diseases Drug Discovery, 897 Independence Ave, Suite 2C, Mountain View, CA 94043, USA. david.swinney@irnd3.org.
authors.forename: Georges
authors.initials: G
authors.lastname: Vauquelin
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D055808:Drug Discovery; D006801:Humans; D007700:Kinetics; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled