Quantifying Global Tolerance of Biochemical Systems Design Implications for Moiety-Transfer Cycles 英文参考文献.docVIP

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Quantifying Global Tolerance of Biochemical Systems Design Implications for Moiety-Transfer Cycles 英文参考文献.doc

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Quantifying Global Tolerance of Biochemical Systems Design Implications for Moiety-Transfer Cycles 英文参考文献

QuantifyingGlobalToleranceofBiochemicalSystems: DesignImplicationsforMoiety-TransferCycles PedroM.B.M.Coelho1,2,ArmindoSalvador3*,MichaelA.Savageau2 1Biological Chemistry Group, Chemistry Department, University of Coimbra, Coimbra, Portugal, 2Biomedical Engineering Department, University of California Davis, Davis,California,UnitedStatesofAmerica,3CenterforNeurosciencesandCellBiology,UniversityofCoimbra,Coimbra,Portugal Abstract Robustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constantwithinsomeneighborhoodofthenormaloperatingregime,leadingtohomeostasis,butthenabruptlybreakdown withpathologicalconsequencesbeyondthisneighborhood.Currently,thereisnogenericapproachtoidentifyingboundaries wherelocalperformancedeterioratesabruptly,andthishashamperedunderstandingofthemolecularbasisofbiological robustness.Hereweintroduceagenericapproachforcharacterizingboundariesbetweenoperationalregimesbasedonthe piecewise power-law representation of the system’s components. This conceptual framework allows us to define ‘‘global tolerance’’astheratiobetweenthenormalvalueofaparameterandthevalueatsuchaboundary.Weillustratetheutilityof thisconceptforaclassofmoiety-transfercycles,whichisawidespreadmoduleinbiology.Ourresultsshowaregionof‘‘best’’ localperformancesurroundedby‘‘poor’’regions;also,selectionforimprovedlocalperformanceoftenpushestheoperating valuesawayfromregimeboundaries,thusincreasingglobaltolerance.Thesepredictionsagreewithexperimentaldatafrom thereducednicotinamideadeninedinucleotidephosphate(NADPH)redoxcycleofhumanerythrocytes. Citation: Coelho PMBM, Salvador A, Savageau MA (2009) Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles.PLoSComputBiol5(3):e1000319.doi:10.1371/journal.pcbi.1000319 Editor:GaryD.Stormo,WashingtonUniversity,UnitedStatesofAmerica ReceivedSeptember30,2008;AcceptedFebruary4,2009;PublishedMarch20,2009 Copyright: ? 2009 Coelho et al. This i