RNA Unwinding by NS3 Helicase A Statistical Approach 英文参考文献.docVIP

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RNA Unwinding by NS3 Helicase A Statistical Approach 英文参考文献.doc

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RNA Unwinding by NS3 Helicase A Statistical Approach 英文参考文献

RNAUnwindingbyNS3Helicase:AStatisticalApproach SrikeshG.Arunajadai* DepartmentofBiostatisticsandAnesthesiology,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Thestudy ofdouble-strandedRNAunwinding byhelicasesis aproblem ofbasic scientificinterest. Onesuchexampleis provided by studies on the hepatitis C virus (HCV) NS3 helicase using single molecule mechanical experiments. HCV currentlyinfectsnearly3%oftheworldpopulationandNS3isaproteinessentialforviralgenomereplication.Theobjective ofthisstudyistomodeltheRNAunwindingmechanismbasedonpreviouslypublisheddataandstudyitscharacteristics and their dependence on force, ATP and NS3 protein concentration. In this work, RNA unwinding by NS3 helicase is hypothesizedtooccurinaseriesofdiscretestepsandthestepsthemselvesoccurringinaccordancewithanunderlying point process. A point process driven change point model is employed to model the RNA unwinding mechanism. The resultsareinlargeagreementwithfindingsinpreviousstudies.Agammadistributionbasedrenewalprocesswasfoundto model well the point process that drives the unwinding mechanism. The analysis suggests that the periods of constant extensionobservedduringNS3activitycanindeedbeclassifiedintopausesandsubpausesandthateachdependonthe ATPconcentration.Thestepsizeisindependentofexternalfactorsandseemstohaveamedianvalueof11.37basepairs. Thestepsthemselvesarecomposedofanumberofsubstepswithanaverageofabout4substepsperstepandanaverage substep size of about 3.7 basepairs. An interestingfinding pertains tothe stepping velocity. Ouranalysis indicates that steppingvelocitymaybeoftwokinds-alowandahighvelocity. Citation:ArunajadaiSG(2009)RNAUnwindingbyNS3Helicase:AStatisticalApproach.PLoSONE4(9):e6937.doi:10.1371/journal.pone.0006937 Editor:GrzegorzKudla,UniversityofEdinburgh,UnitedKingdom ReceivedApril27,2009;AcceptedJuly27,2009;PublishedSeptember22,2009 Copyright:?2009SrikeshG.Arunajadai.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLic