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
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
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