ProteinArchitect Protein Evolution above the Sequence Level 英文参考文献.docVIP

ProteinArchitect:ProteinEvolutionabovetheSequence Level MatthiasHaimel1¤a,KarinPro¨ll1,MichaelRebhan2¤b* 1Department of Bioinformatics, Upper Austrian University of Applied Sciences, Hagenberg, Austria, 2Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland Abstract Background:Whilemanyauthorshavediscussedmodelsandtoolsforstudyingproteinevolutionatthesequencelevel, molecularfunctionisusuallymediatedbycomplex,higherorderfeaturessuchasindependentlyfoldingdomainsandlinear motifs that are based on or embedded in a particular arrangment of features such as secondary structure elements, transmembrane domains and regions with intrinsic disorder. This ‘protein architecture’ can, in its most simplistic representation,bevisualizedasdomainorganizationcartoonsthatcanbeusedtocompareproteinsintermsoftheorderof theirmostlyglobulardomains. Methodology: Here, we describe a visual approach and a webserver for protein comparison that extend the domain organizationcartoonconcept.Bydevelopinganinformation-rich,compactvisualizationofdifferentproteinfeaturesabove the sequence level, potentially related proteins can be compared at the level of propensities for secondary structure, transmembrane domains and intrinsic disorder, in addition to PFAM domains. A public Web server is available at www. ,. Conclusions/Significance: Due to recent advances in sequencing technologies we are now flooded with millions of predictedproteinsthatawaitcomparativeanalysis.Inmanycases,maturetoolsfocusedonrevealinghitswithconsiderable globalorlocalsimilaritytowell-characterizedproteinswillnotbeabletoleadustotestablehypothesesaboutaprotein’s function, or the function of a particular region. The visual comparison of different types of protein features with ProteinArchitect will be useful when assessing the relevance of similarity search hits, to discover subgroups in protein familiesandsuperfamilies,andtounderstandproteinregionswithconservedfeaturesoutsideglobularregions.Therefore, thisapproa