title: Modelling the activation of G-protein coupled receptors by a single drug.
abstract: In this paper, the most popular proposed mechanism for activation of G-protein coupled receptors (GPCRs)--the shuttling mechanism--is modelled mathematically. An asymptotic analysis of this model clarifies the dynamics of the system in the presence of a drug, in particular identifying which reactions dominate during the different timescales. The modelling also reveals challenging behaviour in the form of a peak response. This new mechanism gives simple explanations for complex, possibly misunderstood, behaviour.
authors.affiliation: Centre for Mathematical Medicine, Division of Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, Nottingham NG72RD, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Woodroffe
authors.forename: L J
authors.initials: LJ
authors.lastname: Bridge
authors.forename: J R
authors.initials: JR
authors.lastname: King
authors.forename: S J
authors.initials: SJ
authors.lastname: Hill
mesh_terms: D000465:Algorithms; D055162:Biocatalysis / Q000187:drug effects; D003198:Computer Simulation; D054314:Drug Inverse Agonism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011487:Protein Conformation / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled; D020962:Heterotrimeric GTP-Binding Proteins