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

TitleDBD-Hunter: a knowledge-based method for the prediction of DNA-protein interactions
Publication TypeJournal Article
Year of Publication2008
AuthorsGao, M, Skolnick J
JournalNucleic acids research
Volume36
Pagination3978-92
Date Published2008 Jul
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 approximately 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 DNA-binding protein structures determined in DNA-free (apo) state. We show 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 approximately 1700 structural genomics targets and predict that 37 targets with previously unknown function are likely to be DNA-binding proteins. DBD-Hunter is freely available at http://cssb.biology.gatech.edu/skolnick/webservice/DBD-Hunter/.

PDFhttp://cssb.biology.gatech.edu/skolnick/publications/pdffiles/292.pdf
Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/18515839?dopt=Abstract

Supplementary Data

http://cssb.biology.gatech.edu/skolnick/sup/DBD-Hunter

Alternate JournalNucleic Acids Res.
Citekey292