Classical vs. Stochastic Kinetics Modeling of Biochemical Reaction Systems

¹ The Johns Hopkins University

^* To whom correspondence should be addressed. E-mail: goutsias{at}jhu.edu.

Submitted on July 21, 2006
Revised on September 13, 2006
Accepted on 19 December 2006

	Abstract

We study fundamental relationships between classical and stochastic chemical kinetics for general biochemical systems with elementary reactions. Analytical and numerical investigations show that intrinsic fluctuations may qualitatively and quantitatively affect both transient and stationary system behavior. Thus, we provide a theoretical understanding of the role that intrinsic fluctuations may play in inducing biochemical function. The mean concentration dynamics are governed by differential equations that are similar to the ones of classical chemical kinetics, expressed in terms of the stoichiometry matrix and time-dependent fluxes. However, each flux is decomposed into a macroscopic term, which accounts for the effect of mean reactant concentrations on the rate of product synthesis, and a mesoscopic term, which accounts for the effect of statistical correlations among interacting reactions. We demonstrate that the ability of a model to account for phenomena induced by intrinsic fluctuations may be seriously compromised if we do not include the mesoscopic fluxes. Unfortunately, computation of fluxes and mean concentration dynamics requires intensive Monte Carlo simulation. To circumvent the computational expense, we employ a moment closure scheme, which leads to differential equations that can be solved by standard numerical techniques to obtain more accurate approximations of fluxes and mean concentration dynamics than the ones obtained with the classical approach.

Key Words: biochemical reaction systems, classical chemical kinetics, computational systems biology, stochastic chemical kinetics

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