Mathematical modelling is of prime importance in signal transduction studies, both for drug and receptor classification and for assessing the change in agonist function after a system modification. Two models can be used: empirical and mechanistic models. Empirical models are used to find the mathematical equation that best fits experimental data. These equations can be very useful to quantitatively analyse physiological function although their equation parameters (location, asymptotes, mid-point slope and point of inflection of the corresponding concentration-effect curves) lack physical meaning. Mechanistic models result from applying the physicochemical laws that govern the proposed reaction paths. In the latter case, two approaches can be followed: equilibrium models and dynamic or kinetic models. Mechanistic models differ from empirical ones in the existence of a correspondence between the equation parameters and the chemical constants of the biological processes. In the present project, we aim at developing a comprehensive series of mathematical models for a quantitative description of the signal transduction mechanisms associated to G protein-coupled receptors, i.e. receptor reserve, partial agonism, constitutive activity, inverse agonism, receptor dimerization, cooperativity, receptor desenzitation, G protein activation and GTPase-activating proteins; as well as for the prediction of the final response of these complex systems when a perturbation (a change in the concentration of one of the reactants or in the constants that regulate the equilibria between the species) occurs. Each of the proposed models will not be considered as an isolated element but as an integrated component within a general theoretical framework. The ultimate reason of the proposed work is our belief that a systematic investigation on this field can help to foster the development of more effective drugs to improve human health.
|Effective start/end date||13/12/04 → 13/12/07|