DomPep—A General Method for Predicting Modular Domain-Mediated Protein-Protein Interactions 英文参考文献.docVIP

DomPep—AGeneralMethodforPredictingModular Domain-MediatedProtein-ProteinInteractions LeiLi1,BingZhao1,JunDu2,KaizhongZhang2,CharlesX.Ling2,ShawnShun-ChengLi1* 1DepartmentofBiochemistry,Siebens-DrakeMedicalResearchInstitute,SchulichSchoolofMedicineandDentistry,TheUniversityofWesternOntario,London,Ontario, Canada,2DepartmentofComputerScience,TheUniversityofWesternOntario,London,Ontario,Canada Abstract Protein-proteininteractions(PPIs)arefrequentlymediatedbythebindingofamodulardomaininoneproteintoashort, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulationofawealthofinteractiondataformodularinteractiondomains.Althoughseveralcomputationalprograms havebeendevelopedtopredictmodulardomain-mediatedPPIevents,theyareoftenrestrictedtoagivendomaintype.We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. ProteomicbindingdatawereemployedtodetermineasimpleyetnovelparameterLigand-BindingSimilaritywhich,inturn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental bindingdataandthosewithout.UsingthePDZandSH2domainfamiliesastestcases,weshowthatDomPepcanpredict PPIs with accuracies superior to existing methods. To evaluate DomPep as a discovery tool, we deployed DomPep to identify interactions mediated by three human PDZ domains. Subsequent in-solution binding assays validated the high accuracyofDomPepinpredictingauthenticPPIsattheproteomescale.BecauseDomPepmakesuseofonlyinteraction dataandtheprimarysequenceofadomain,itcanbereadilyexpandedtoincludeothertypesofmodulardomains. Citation: Li L, Zhao B, Du J, Zhang K, Ling CX, et al. (2011) DomPep—A General Method for