Chen C Y, Cordeaux Y, Hill S J, King J R
Centre for Mathematical Medicine, Division of Theoretical Mechanics, School of Mathematical Science, The University of Nottingham, Nottingham, UK.
Bull Math Biol. 2003 Sep;65(5):933-58. doi: 10.1016/S0092-8240(03)00055-7.
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.
构建了一个数学模型来研究受体与G蛋白的杂乱偶联，并模拟导致细胞内多种效应器途径激活的事件。该模型旨在更好地理解决定药物疗效和效力的因素。假设受体可以存在于多种构象状态，并考虑激动剂特异性构象，构建了一个常微分方程组，随后预测了依赖途径的激动剂疗效和效力顺序。还给出了受体和G蛋白区室化的一个简单案例，用当前模型来说明空间异质性对预测反应的影响。
