Modelling of signalling via G-protein coupled receptors: pathway-dependent agonist potency and efficacy

Abstract

A mathematical model is constructed to study promiscuous coupling of receptors to G-proteins and to simulate events leading to the activation of multiple effector pathways within a cell. The model is directed at a better understanding of the factors that determine the efficacy and potency of a drug. Assuming that the receptors can exist in multiple conformational states, and allowing for agonist specific conformation, a system of ordinary differential equations is constructed and subsequently pathway-dependent agonist efficacy and potency order is predicted. A simple case of the compartmentalization of receptors and G-proteins is also given, using the current model to illustrate the effects of spatial heterogeneity on the predicted response.