Theory and Method of a Priori Computation of Catalytic Acts of Aspartic and Serine Proteinases

Abstract

Theory of enzymatic catalysis based on the new concept of structure-functional organisation of proteins is developed. Previously it has been shown [1], that dynamic conformational properties of a polypeptide chain, manifesting in the folding process cannot be described using current ideas of classical equilibrium thermodynamics. Novel principles of non-linear nonequilibrium thermodynamics (Prigogine physics) have been introduced, giving for the first time explanation to all characteristic features of protein folding process (stochastic mechanism, short time and precision of self-assembling) and of protein interaction with other molecules [1–3]. These principles formed the base for a quantitative approach to the investigations of mechanism of enzymatic catalysis. In a spontaneous enzymatic reaction, decisive contribution is made by irreversible fluctuations (bifurcations), characteristic for non-equilibrium dissipative ensembles. These fluctuations drastically change the evolution of the system, producing new energetically favourable states due to the formation of specific stabilising contacts with other parts of a protein molecule in the folding process or with a substrate molecule in enzymatic reaction. It was shown [4], that the process of spontaneous transformations of thermal energy of irreversible fluctuations into conformational and electronic energy of enzymatic catalysis cannot have counterparts in the model chemical (congruent) reactions governed by completely different mechanisms of equilibrium thermodynamics and statistical physics.