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dc.contributor.authorGao, Mu
dc.contributor.authorSkolnick, Jeffrey
dc.date.accessioned2009-01-28T15:06:35Z
dc.date.available2009-01-28T15:06:35Z
dc.date.issued2008-05-31
dc.identifier.citationNucleic Acids Research 2008 36(12):3978-3992en
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/1853/26729
dc.description© 2008 The Authors. Published byOxford University Press. The definitive version is available online at: http://nar.oxfordjournals.org/cgi/content/full/36/12/3978en
dc.descriptiondoi:10.1093/nar/gkn332
dc.description.abstractThe structures of DNA–protein complexes have illuminated the diversity of DNA–protein binding mechanisms shown by different protein families. This lack of generality could pose a great challenge for predicting DNA–protein interactions. To address this issue, we have developed a knowledge-based method, DNA-binding Domain Hunter (DBD-Hunter), for identifying DNA-binding proteins and associated binding sites. The method combines structural comparison and the evaluation of a statistical potential, which we derive to describe interactions between DNA base pairs and protein residues. We demonstrate that DBD-Hunter is an accurate method for predicting DNA-binding function of proteins, and that DNA-binding protein residues can be reliably inferred from the corresponding templates if identified. In benchmark tests on ~4000 proteins, our method achieved an accuracy of 98% and a precision of 84%, which significantly outperforms three previous methods. We further validate the method on DNAbinding protein structures determined in DNA-free (apo) state. Weshow that the accuracy of our method is only slightly affected on apo-structures compared to the performance on holo-structures cocrystallized with DNA. Finally, we apply the method to ~1700 structural genomics targets and predict that 37 targets with previously unknown function are likely to be DNA-binding proteins.en
dc.language.isoen_USen
dc.publisherGeorgia Institute of Technologyen
dc.subjectComputational biologyen
dc.subjectProtein structureen
dc.subjectDNA-binding proteinsen
dc.subjectKnowledge-based systemsen
dc.titleDBD-Hunter: a knowledge-based method for the prediction of DNA protein interactionsen
dc.typeArticleen
dc.contributor.corporatenameGeorgia Institute of Technology. Center for the Study of Systems Biology
dc.publisher.originalOxford University Press


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