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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DOI:
10.1093/nar/gkn332
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发表时间:
2008-07
影响因子:
14.9
通讯作者:
Skolnick, Jeffrey
Skolnick, Jeffrey
中科院分区:
生物学2区
文献类型:
--
作者:
Gao, Mu;Skolnick, Jeffrey

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DNA - 蛋白质复合物的结构阐明了不同蛋白质家族所示的DNA - 蛋白结合机制的多样性。基于DNA结合结构域(DBD猎人)的方法,用于识别DNA结合蛋白和相关的结合位点。我们得出的统计潜力的评估是为了描述DNA碱基对和蛋白质保留之间的相互作用。从相应的模板中推断出约4000蛋白的基准测试,我们的方法的精度为98%,精度为84%三种方法。最终,我们将方法应用于约1700个结构基因组学靶标,并预测37个具有以前未知功能的靶标可能是DNA结合蛋白。 DBD-Hunter免费提供,请访问http://cssb.biology.gatech.edu/skolnick/webservice/dbd-hunter/。
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 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 ∼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/.
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