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Computational Design of a DNA- and Fc-Binding Fusion Protein英文文献资料.doc

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Computational Design of a DNA- and Fc-Binding Fusion Protein英文文献资料

HindawiPublishingCorporation AdvancesinBioinformatics Volume2011,ArticleID457578,7pages doi:10.1155/2011/457578 ResearchArticle ComputationalDesignofaDNA-andFc-BindingFusionProtein JonasWinkler, FilippoLedda, 1 GiulianoArmano, andDominikHeider 2 J.NikolajDybowski, OliverKuhn, 1 1 1 2 1 DepartmentofBioinformatics,CenterforMedicalBiotechnology,UniversityofDuisburg-Essen,Universitaetsstraβ e1-5, 45117Essen,Germany 2 DepartmentofElectricalandElectronicEngineering,UniversityofCagliari,Piazzad’Armi,09123Cagliari,Italy CorrespondenceshouldbeaddressedtoDominikHeider,dominik.heider@uni-due.de Received29April2011;Revised16June2011;Accepted22June2011 AcademicEditor:ShandarAhmad Copyright?2011JonasWinkleretal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Computationaldesignofnovelproteinswithwell-de?nedfunctionsisanongoingtopicincomputationalbiology.Inthiswork,we generatedandoptimizedanewsyntheticfusionproteinusinganevolutionaryapproach.Theoptimizationwasguidedbydirected evolutionbasedonhydrophobicityscores,molecularweight,andsecondarystructurepredictions.Severalmethodswereusedto re?nethemodelsbuiltfromtheresultingsequences.Wehavesuccessfullycombinedtwounrelatednaturallyoccurringbinding sites,theimmunoglobinFc-bindingsiteoftheZdomainandtheDNA-bindingmotifofMyoDbHLH,intoanovelstableprotein. 1.Introduction proteins may have structural homology although this is not a prerequisite. Prominent examples are the antifreeze glycoproteins[6],proteinphosphatases[7],andglutaminyl cyclases[8]. Protein design methods use trial and error or more sophisticated methods like directed evolution or inverse foldingtogeneratenovelsca?oldsorto?ndnovelprotein sequencesfoldingintoade?nedsca?old,respectively.Given theintimaterelationshipbetweenaprotein’sstructureand function,awaytodesignproteinswithtargetedproperties istostartfromadesiredstructurea