蛋白rna结构与功能（protein rna structure and function）

DDobbsISU BCB444 544X ProteinStructure Function 1 11 4 05ProteinStructure Function DDobbsISU BCB444 544X ProteinStructure Function 2 Announcements Exam2 Hasbeengraded WillbereturnedatendofclasstodayGradestatistics 444Average 81 100544Average 100 118Questions DDobbsISU BCB444 544X ProteinStructure Function 3 Announcements BCB544Projects ImportantDates Nov2Wednoon ProjectproposalsduetoDavid DrenaNov4FriPM Approvals responses tentativepresentationscheduletostudentsDec2Frinoon WrittenprojectreportsdueDec5 7 8 9class lab OralPresentations 20 Dec15Thurs FinalExam DDobbsISU BCB444 544X ProteinStructure Function 4 BioinformaticsSeminars Nov4Fri12 10PMBCBFacultySeminarinE164LagoHowtodosequencealignmentsonparallelcomputersSrinivasAluru ECprE Chair BCBProgramhttp www bcb iastate edu courses BCB691F2005 htmlNextweek Nov10Thurs3 40PMComSSeminarin223AtanasoffComputationalEpidemiologyArminR Mikler Univ NorthTexashttp www cs iastate edu colloq t3 DDobbsISU BCB444 544X ProteinStructure Function 5 BioinformaticsSeminars CORRECTION Weekafternext BakerCenter BCBSeminars seminarabstractsavailableatabovelink Nov14Mon1 10PMDougBrutlag StanfordDiscoveringtranscriptionfactorbindingsitesNov15Tues1 10PMIlyaVakser UnivKansasModelingprotein proteininteractionsbothseminarswillbeinHoweHallAuditorium DDobbsISU BCB444 544X ProteinStructure Function 6 RNAStructure Function PredictionProteinStructure Function MonReview promoterpredictionRNAstructure functionWedRNAstructureprediction2 3 structurepredictionmiRNA targetprediction Lab10Fri afewmorewordsre AlgorithmsProteinstructure function DDobbsISU BCB444 544X ProteinStructure Function 7 ReadingAssignment forFri Mon MountBioinformaticsChp10Proteinclassification structurepredictionhttp www bioinformaticsonline org ch ch10 index htmlpp 409 491CkErrata http www bioinformaticsonline org help errata2 htmlOther Thatshouldbeplenty DDobbsISU BCB444 544X ProteinStructure Function 8 Reviewlastlecture RNAStructurePrediction DDobbsISU BCB444 544X ProteinStructure Function 9 miRNAandRNAipathways CBurge2005 DDobbsISU BCB444 544X ProteinStructure Function 10 miRNAChallengesforComputationalBiology FindthegenesencodingmicroRNAs Predicttheirregulatorytargets IntegratemiRNAsintogeneregulatorypathways networks ComputationalPredictionofMicroRNAGenes Targets CBurge2005 Needtomodifytraditionalparadigmof transcriptionalcontrol primarilybyprotein DNAinteractionstoincludemiRNAregulatorymechanisms DDobbsISU BCB444 544X ProteinStructure Function 11 RNAstructurepredictionstrategies Energyminimization thermodynamics 2 Comparativesequenceanalysis co variation 3 Combinedexperimental computational Secondarystructureprediction DDobbsISU BCB444 544X ProteinStructure Function 12 Secondarystructurepredictionstrategies Energyminimization thermodynamics Algorithm Dynamicprogrammingtofindhighprobabilitypairs also somegeneticalgorithms Software Mfold ZukerViennaRNAPackage HofackerRNAstructure MathewsSfold Ding Lawrence RKnight2005 DDobbsISU BCB444 544X ProteinStructure Function 13 Secondarystructurepredictionstrategies 2 Comparativesequenceanalysis co variation Algorithms MutualinformationStochasticcontext freegrammarsSoftware ConStructAlifoldPfoldFOLDALIGNDynalign RKnight2005 DDobbsISU BCB444 544X ProteinStructure Function 14 Secondarystructurepredictionstrategies 3 Combinedexperimental computational Experiment Mapsingle strandedvsdouble strandedregionsinfoldedRNAHow Enzymes S1nuclease T1RNaseChemicals kethoxal DMS RKnight2005 DDobbsISU BCB444 544X ProteinStructure Function 15 ExperimentalRNAstructuredetermination X raycrystallographyNMRspectroscopyEnzymatic chemicalmapping Moleculargeneticanalyses DDobbsISU BCB444 544X ProteinStructure Function 16 1 Energyminimizationmethod Whataretheassumptions Nativetertiarystructureor fold ofanRNAmoleculeis oneof its lowest freeenergyconfiguration s Gibbsfreeenergy Ginkcal molat37 C equilibriumstabilityofstructurelowervalues negative aremorefavorableIsthisassumptionvalid invivo thismaynothold butwedon treallyknow DDobbsISU BCB444 544X ProteinStructure Function 17 Freeenergyminimization Whataretherules Whatgiveshere CStaben2005 DDobbsISU BCB444 544X ProteinStructure Function 18 Energyminimizationcalculations Base stackingiscritical Tinoccoetal CStaben2005 DDobbsISU BCB444 544X ProteinStructure Function 19 Nearest neighborparameters Mostmethodsforfreeenergyminimizationusenearest neighborparameters derivedfromexperiment forpredictingstabilityofanRNAsecondarystructure intermsof Gat37 C mostavailablesoftwarepackagesusethesamesetofparameters Mathews Sabina Zuker Turner 1999 DDobbsISU BCB444 544X ProteinStructure Function 20 Energyminimization calculations TotalfreeenergyofaspecificconformationforaspecificRNAmolecule sumofincrementalenergytermsfor helicalstacking sequencedependent loopinitiationunpairedstacking favorable increments are 0 Fig6 3Baxevanis Ouellette2005 DDobbsISU BCB444 544X ProteinStructure Function 21 ButhowmanypossibleconformationsforasingleRNAmolecule Hugenumber Zukerestimates 1 8 NpossiblesecondarystructuresforasequenceofNnucleotidesfor100nts smallRNA 3X1025structures Solution Notexhaustiveenumeration DynamicprogrammingO N3 intimeO N2 inspace storageiffpseudoknotsexcluded otherwise O N6 timeO N4 space DDobbsISU BCB444 544X ProteinStructure Function 22 Algorithmsbasedonenergyminimization ForoutlineofalgorithmusedinMfold includingdescriptionofdynamicprogrammingrecursion pleasevisitMichaelZuker slecture http www bioinfo rpi edu zukerm lectures RNAfold htmlFromthissite youmayalsodownloadhislectureaseitherPDForPSfile Hmmm somethingbasedonthismightmakeaninteresting FinalExam question howcouldoneapplydynamicprogrammingapproacheslearnedinfirsthalfofcoursetoRNAstructurepredictionproblem DDobbsISU BCB444 544X ProteinStructure Function 23 2 Comparativesequenceanalysis co variation Twobasicapproaches AlgorithmsconstrainedbyinitialalignmentMuchfaster butnotasrobustasunconstrainedBase pairingprobabilitiesdeterminedbyapartitionfunctionAlgorithmsnotconstrainedbyinitialalignmentGeneticalgorithmsoftenusedforfindinganalignment setofstructures DDobbsISU BCB444 544X ProteinStructure Function 24 RNASecondarystructureprediction Performance Howevaluate Notmanyexperimentallydeterminedstructurescurrently 50 arerRNAstructuresso GoldStandard inabsenceoftertiarystructure comparewithpredictedRNAsecondarystructurewiththatdeterminedbycomparativesequenceanalysis usingBenchmarkDatasetsNOTE Base pairspredictedbycomparativesequenceanalysisforlarge smallsubunitrRNAsare97 accuratewhencomparedwithhighresolutioncrystalstructures Gutell Pace DDobbsISU BCB444 544X ProteinStructure Function 25 RNASecondarystructureprediction Performance Energyminimization viadynamicprogramming 73 avg predictionaccuracy singlesequence2 Comparativesequenceanalysis97 avg predictionaccuracy multiplesequences e g highlyconservedrRNAs muchlowerifsequenceconservationislower orfewersequencesareavailableforalignment3 Combined recentdevelopments combinethermodynamics co variation experimentalconstraints IMPROVEDRESULTS DDobbsISU BCB444 544X ProteinStructure Function 26 RNAstructurepredictionstrategies Requires craft significantuserinput insightExtensivecomparativesequenceanalysistopredicttertiarycontacts co variation e g MANIP WesthofUseexperimentaldatatoconstrainmodelbuildinge g MC CYM MajorHomologymodelingusingsequencealignment referencetertiarystructure notmanyofthese Lowresolutionmolecularmechanicse g yammp Harvey Tertiarystructureprediction DDobbsISU BCB444 544X ProteinStructure Function 27 NewToday ProteinStructure Function DDobbsISU BCB444 544X ProteinStructure Function 28 ProteinStructure Function Proteinstructure primarilydeterminedbysequenceProteinfunction primarilydeterminedbystructureGlobularproteins compacthydrophobiccore hydrophilicsurfaceMembraneproteins specialhydrophobicsurfacesFoldedproteinsareonlymarginallystableSomeproteinsdonotassumeastable fold untiltheybindtosomething IntrinsicallydisorderedPred