Modelling the activation of G-protein coupled receptors by a single drug.
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.
Woodroffe
P J
PJ
Centre for Mathematical Medicine, Division of Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, Nottingham NG72RD, UK.
Bridge
L J
LJ
King
J R
JR
Hill
S J
SJ
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
D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled; D020962:Heterotrimeric GTP-Binding Proteins