DBD-Hunter: a knowledge-based method for the prediction of DNA protein interactions

dc.contributor.author Gao, Mu
dc.contributor.author Skolnick, Jeffrey
dc.contributor.corporatename Georgia Institute of Technology. Center for the Study of Systems Biology
dc.date.accessioned 2009-01-28T15:06:35Z
dc.date.available 2009-01-28T15:06:35Z
dc.date.issued 2008-05-31
dc.description © 2008 The Authors. Published byOxford University Press. The definitive version is available online at: http://nar.oxfordjournals.org/cgi/content/full/36/12/3978 en
dc.description doi:10.1093/nar/gkn332
dc.description.abstract The 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.identifier.citation Nucleic Acids Research 2008 36(12):3978-3992 en
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/1853/26729
dc.language.iso en_US en
dc.publisher Georgia Institute of Technology en
dc.publisher.original Oxford University Press
dc.subject Computational biology en
dc.subject Protein structure en
dc.subject DNA-binding proteins en
dc.subject Knowledge-based systems en
dc.title DBD-Hunter: a knowledge-based method for the prediction of DNA protein interactions en
dc.type Text
dc.type.genre Article
dspace.entity.type Publication
local.contributor.author Skolnick, Jeffrey
local.contributor.corporatename College of Sciences
local.contributor.corporatename School of Biological Sciences
local.contributor.corporatename Center for the Study of Systems Biology
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