Title:
DBD-Hunter: a knowledge-based method for the prediction of DNA protein interactions
DBD-Hunter: a knowledge-based method for the prediction of DNA protein interactions
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Gao, Mu
Skolnick, Jeffrey
Skolnick, Jeffrey
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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.
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2008-05-31
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