In many stochastic simulations of biochemical reaction networks, it is desirable to "coarse grain" the reaction set, removing fast reactions while retaining the correct system dynamics. Various coarse-graining methods have been proposed, but it remains unclear which methods are reliable and which reactions can safely be eliminated. We address these issues for a model gene regulatory network that is particularly sensitive to dynamical fluctuations: a bistable genetic switch. We remove protein-DNA and/or protein-protein association-dissociation reactions from the reaction set using various coarse-graining strategies. We determine the effects on the steady-state probability distribution function and on the rate of fluctuation-driven switch flipping transitions. We find that protein-protein interactions may be safely eliminated from the reaction set, but protein-DNA interactions may not. We also find that it is important to use the chemical master equation rather than macroscopic rate equations to compute effective propensity functions for the coarse-grained reactions.

Includes erratum: J. Chem. Phys. 128 (2008) 169901 1-1
J. Chem. Phys.
Biochemical Networks

Morelli, M. J., Allen, R. J., Tanase-Nicola, S., & ten Wolde, P. R. (2008). Eliminating fast reactions in stochastic simulations of biochemical networks : a bistable genetic switch. J. Chem. Phys., 128(Article number: 45105), 1–13. doi:10.1063/1.2821957