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dc.contributor.authorDai, Liang
dc.contributor.authorYang, Yuedong
dc.contributor.authorKim, Hyung Rae
dc.contributor.authorZhou, Yaoqi
dc.date.accessioned2017-05-03T15:56:04Z
dc.date.available2017-05-03T15:56:04Z
dc.date.issued2010
dc.date.modified2014-05-28T22:26:30Z
dc.identifier.issn10970134
dc.identifier.doi10.1002/prot.22746
dc.identifier.urihttp://hdl.handle.net/10072/57416
dc.description.abstractDesigning a protein sequence that will fold into a predefined structure is of both practical and fundamental interest. Many successful, computational designs in the last decade resulted from improved understanding of hydrophobic and polar interactions between side chains of amino acid residues in stabilizing protein tertiary structures. However, the coupling between main-chain backbone structure and local sequence has yet to be fully addressed. Here, we attempt to account for such coupling by using a sequence profile derived from the sequences of five residue fragments in a fragment library that are structurally matched to the five-residue segments contained in a target structure. We further introduced a term to reduce low complexity regions of designed sequences. These two terms together with optimized reference states for amino-acid residues were implemented in the RosettaDesign program. The new method, called RosettaDesign-SR, makes a 12% increase (from 34 to 46%) in fraction of proteins whose designed sequences are more than 35% identical to wild-type sequences. Meanwhile, it reduces 8% (from 22% to 14%) to the number of designed sequences that are not homologous to any known protein sequences according to psiblast. More importantly, the sequences designed by RosettaDesign-SR have 2-3% more polar residues at the surface and core regions of proteins and these surface and core polar residues have about 4% higher sequence identity to wild-type sequences than by RosettaDesign. Thus, the proteins designed by RosettaDesign-SR should be less likely to aggregate and more likely to have unique structures due to more specific polar interactions.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent609080 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherWILEY-LISS, INC.
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom2338
dc.relation.ispartofpageto2348
dc.relation.ispartofissue10
dc.relation.ispartofjournalProteins: Structure, Function, and Bioinformatics
dc.relation.ispartofvolume78
dc.rights.retentionY
dc.subject.fieldofresearchBioinformatics
dc.subject.fieldofresearchMathematical Sciences
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchInformation and Computing Sciences
dc.subject.fieldofresearchcode060102
dc.subject.fieldofresearchcode01
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode08
dc.titleImproving computational protein design by using structure-derived sequence profile
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2010 Wiley Periodicals, Inc. This is the accepted version of the following article: Improving computational protein design by using structure-derived sequence profile, Proteins: Structure, Function, and Bioinformatics, Vol. 78(10), 2010, pp. 2338-2348, which has been published in final form at dx.doi.org/10.1002/prot.22746.
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorZhou, Yaoqi
gro.griffith.authorYang, Yuedong


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