[工程科技]Eliminatingfastreactionsinstochasticsimulationsofbiochemicalnetworksabistablegen.pdfVIP

Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch Marco J. Morelli,1 Rosalind J. Allen,2 Sorin T˘anase-Nicola,1 and Pieter Rein ten Wolde1 1FOM Institute for Atomic and Molecular Physics, 7 Kruislaan 407, 1098 SJ Amsterdam, The Netherlands 0 2 0 SUPA, School of Physics, The University of Edinburgh, James Clerk Maxwell Building, 2 The King’s Buildings, Mayfield Road, Edinburgh EH9 3JZ, UK v o (Dated: February 2, 2008) N 8 In many stochastic simulations of biochemical reaction networks, it is desir- 2 able to “coarse-grain” the reaction set, removing fast reactions while retain- ] M ing the correct system dynamics. Various coarse-graining methods have been Q . proposed, but it remains unclear which methods are reliable and which re- o i actions can safely be eliminated. We address these issues for a model gene b - q regulatory network that is particularly sensitive to dynamical fluctuations: [ 1 a bistable genetic switch. We remove protein-DNA and/or protein-protein v association-dissociation reactions from the reaction set, using various coarse- 2 1 5 graining strategies. We determine the effects on the steady-state probability 4 . distribution function and on the rate of fluctuation-driven switch flipping tran- 1 1 sitions. We find that protein-protein interactions may be safely eliminated from 7 0 the reaction set, but protein-DNA interact