Bridging the gap between stochastic and deterministic regimes in the kinetic simulations of the biochemical reaction networks.
The biochemical reaction networks include elementary reactions differing by many orders of magnitude in the numbers of molecules involved. The kinetics of reactions involving small numbers of molecules can be studied by exact stochastic simulation. This approach is not practical for the simulation of metabolic processes because of the computational cost of accounting for individual molecular collisions. We present the "maximal time step method," a novel approach combining the Gibson and Bruck algorithm with the Gillespie tau-leap method. This algorithm allows stochastic simulation of systems composed of both intensive metabolic reactions and regulatory processes involving small numbers of molecules. The method is applied to the simulation of glucose, lactose, and glycerol metabolism in Escherichia coli. The gene expression, signal transduction, transport, and enzymatic activities are modeled simultaneously. We show that random fluctuations in gene expression can propagate to the level of metabolic processes. In the cells switching from glucose to a mixture of lactose and glycerol, random delays in transcription initiation determine whether lactose or glycerol operon is induced. In a small fraction of cells severe decrease in metabolic activity may also occur. Both effects are epigenetically inherited by the progeny of the cell in which the random delay in transcription initiation occurred.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Jacek
J
Puchałka
Andrzej M
AM
Kierzek
D001671:Biochemistry / Q000379:methods; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D004926:Escherichia coli / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007700:Kinetics; D007785:Lactose / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013269:Stochastic Processes; D013997:Time Factors
D009097:Multienzyme Complexes; D005947:Glucose; D007785:Lactose; D005990:Glycerol