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Analyzing Effects of Naturally Occurring Missense Mutations英文文献资料.doc

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Analyzing Effects of Naturally Occurring Missense Mutations英文文献资料

HindawiPublishingCorporation ComputationalandMathematicalMethodsinMedicine Volume2012,ArticleID805827,15pages doi:10.1155/2012/805827 ReviewArticle AnalyzingEffectsofNaturallyOccurringMissenseMutations LinWang, andEmilAlexov ZheZhang,1,2MariaA.Miteva,2 1 1 1 2 ComputationalBiophysicsandBioinformatics,DepartmentofPhysicsandAstronomy,ClemsonUniversity,SC29634,USA Universit′eParisDiderot,SorbonneParisCit′e,Mol′eculesTh′erapeutiquesInSilico,InsermUMR-S973,35rueHeleneBrion, 75013Paris,France CorrespondenceshouldbeaddressedtoEmilAlexov,ealexov@ Received21December2011;Revised1February2012;Accepted1February2012 AcademicEditor:GabrielaMustataWilson Copyright?2012ZheZhangetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Single-pointmutationingenome,forexample,single-nucleotidepolymorphism(SNP)orraregeneticmutation,isthechangeofa singlenucleotideforanotherinthegenomesequence.Someofthemwillproduceanaminoacidsubstitutioninthecorresponding proteinsequence(missensemutations);otherswillnot.Thispaperfocusesongeneticmutationsresultinginachangeinthe aminoacidsequenceofthecorrespondingproteinandhowtoassesstheire?ectsonproteinwild-typecharacteristics.Theexisting methodsandapproachesforpredictingthee?ectsofmutationonproteinstability,structure,anddynamicsareoutlinedand discussedwithrespecttotheirunderlyingprinciples.Availableresources,eitherasstand-aloneapplicationsorwebservers,are pointedoutaswell.Itisemphasizedthatunderstandingthemolecularmechanismsbehindthesee?ectsduetothesemissense mutationsisofcriticalimportancefordetectingdisease-causingmutations.Thepaperprovidesseveralexamplesoftheapplication of 3D structure-based methods to model the e?ects of protein stability and protein-protein interactions caused by missense mutationsaswell. 1.Introduction Ontheothersideofthespectrumarenonsynonymous SNPs (nsSNPs), which cau