Eliminating fast reactions in stochastic simulations of biochemical networks: A bistable genetic switch

Marco J. Morelli, Rosalind J. Allen, Sorin Tanase-Nicola, Pieter Rein ten Wolde

Research output: Contribution to journalArticlepeer-review

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. (C) 2008 American Institute of Physics.

Original languageEnglish
Article number045105
Pages (from-to)-
Number of pages13
JournalThe Journal of Chemical Physics
Volume128
Issue number4
DOIs
Publication statusPublished - 28 Jan 2008

Keywords

  • COUPLED CHEMICAL-REACTIONS
  • REPRESSOR
  • EQUILIBRIUM
  • ALGORITHM
  • KINETICS
  • SYSTEMS
  • MODELS

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