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1、蛋白質(zhì)結(jié)構(gòu)預(yù)測(一)ProteinStructurePrediction(I)1ProteinStructurePredictionFromSequencetoNativeStructure2ProteinStructurePredictionPSI-BLAST3ProteinStructurePrediction4MultipleSequenceAlignmentToolsClustalWMultiplesequencealignmentsreveal:conservationofindividualresiduesconservationofregions
2、differenceswithinproteinfamilies5ToolsHMMerProfileForeachpositionalongthesequence,tabulatehowofteneachtypeofaminoacidoccur(include‘.’forgap)TheprofileisalwaysofsizeNx21,nomatterhowmanysequencesareconsidered6ProteinStructurePrediction7SecondaryStructurePredictionGivenaproteinsequence
3、a1a2…aN,secondarystructurepredictionaimsatdefiningthestateofeachaminoacidaiasbeingeitherH(helix),E(extendedstrand),orO(other)(Somemethodshave4states:H,E,Tforturns,andOforother).ThequalityofsecondarystructurepredictionismeasuredwithaQindex(Qhelix,Qstrand,Qcoil)orQ3.Q3isthepercentofre
4、siduesthatmatch“reality”(X-raystructure).8SecondaryStructurePredictionAminoacidsequenceActualSecondaryStructureQ3=22/29=76%Q3=22/29=76%ALHEASGPSVILFGSDVTVPPASNAEQAKhhhhhooooeeeeoooeeeooooohhhhhohhhooooeeeeoooooeeeooohhhhhhhhhhhoooohhhhooohhhooooohhhhh(usefulprediction)(terriblepredi
5、ction)Q3forrandompredictionis33%Secondarystructureassignmentinrealproteinsisuncertaintoabout10%.Therefore,a“perfect”predictionwouldhaveQ3=90%.LimitationsofQ3(Q3=Npredicted?100%/Nobserved)9SecondaryStructurePredictionChou-FasmanMethodStartbycomputingaminoacidspropensitiestobelongtoag
6、iventypeofsecondarystructure:Propensities>1meanthattheresiduetypeiislikelytobefoundinthecorrespondingsecondarystructuretype.10Chou-FasmanMethod參數(shù)值P?、P?和Pt是分別在原有相應(yīng)值的基礎(chǔ)上乘以100得到SecondaryStructurePrediction11SecondaryStructurePredictionChou-FasmanMethodHelixprediction沿著蛋白質(zhì)序列尋找?螺旋核，相鄰的6個
7、殘基中如果有至少4個殘基傾向于形成?螺旋，即有4個殘基對應(yīng)的P?>100，則認(rèn)為是螺旋核。然后從螺旋核向兩端延伸，直至四肽片段P?的平均值小于100為止。按上述方式找到的片段長度大于5，并且P?的平均值大于P?的平均值，那么這個片段的二級結(jié)構(gòu)就被預(yù)測為?螺旋。此外，不容許Pro在螺旋內(nèi)部出現(xiàn)，但可出現(xiàn)在C末端以及N端的前三位，這也用于終止螺旋的延伸。12SecondaryStructurePredictionChou-FasmanMethodStrandPrediction如果相鄰6個殘基中若有4個傾向于形成β折疊，即有4個殘基對應(yīng)的P?>100，則認(rèn)為是折疊
8、核。折疊核向兩端延伸直至4個殘基P?的
