Potential Energy Landscape and Robustness of a Gene Regulatory Network Toggle Switch 英文参考文献.docVIP

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Potential Energy Landscape and Robustness of a Gene Regulatory Network Toggle Switch 英文参考文献.doc

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Potential Energy Landscape and Robustness of a Gene Regulatory Network Toggle Switch 英文参考文献

PotentialEnergyLandscapeandRobustness ofaGeneRegulatoryNetwork:ToggleSwitch Keun-Young Kim1,Jin Wang1,2,3* 1DepartmentofPhysicsandAstronomy,StateUniversityofNewYorkStonyBrook,StonyBrook,NewYork,UnitedStatesofAmerica,2DepartmentofChemistry,State UniversityofNewYorkStonyBrook,StonyBrook,NewYork,UnitedStatesofAmerica,3StateKeyLaboratoryofElectroanalyticalChemistry,ChangchunInstituteofApplied Chemistry,ChineseAcademyofSciences,Changchun,Jilin,People’sRepublicofChina Finding a multidimensional potential landscape is the key for addressing important global issues, such as the robustness of cellular networks. We have uncovered the underlying potential energy landscape of a simple gene regulatory network: a toggle switch. This was realized by explicitly constructing the steady state probability of the geneswitchintheproteinconcentrationspaceinthepresenceoftheintrinsicstatisticalfluctuationsduetothesmall numberofproteinsinthecell.Weexploredtheglobalphasespaceforthesystem.Wefoundthattheproteinsynthesis rateandtheunbindingrateofproteinstothegeneweresmallrelativetotheproteindegradationrate;thegeneswitch ismonostablewithonlyonestablebasinofattraction.Whenboththeproteinsynthesisrateandtheunbindingrateof proteinstothegenearelargecomparedwiththeproteindegradationrate,twoglobalbasinsofattractionemergefor a toggle switch. These basins correspond to the biologically stable functional states. The potential energy barrier between the two basins determines the time scale of conversion from one to the other. We found as the protein synthesis rate and protein unbinding rate to the gene relative to the protein degradation rate became larger, the potentialenergybarrierbecamelarger.Thisalsocorrespondedtosystemswithlessnoiseorthefluctuationsonthe proteinnumbers.Itleadstotherobustnessofthebiologicalbasinsofthegeneswitches.Thetechniqueusedhereis generalandcanbeappliedtoexplorethepotentialenergylandscapeofthegenenetworks. Citation:KimKY,WangJ(2007)Potentialenergylandscapeandrobustnessofagenereg