title: Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch.
abstract: 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.
authors.affiliation: FOM Institute for Atomic and Molecular Physics, Kruislaan 407, 1098 SJ Amsterdam, The Netherlands.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Morelli
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Allen
authors.forename: Sorin
authors.initials: S
authors.lastname: Tănase-Nicola
authors.forename: Pieter Rein
authors.initials: PR
authors.lastname: ten Wolde
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D011336:Probability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D011506:Proteins; D004247:DNA