Binding site prediction for protein-protein interactions and novel motif discovery using re-occurring polypeptide sequences.

Binding site prediction for protein-protein interactions and novel motif discovery using re-occurring polypeptide sequences.
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使用重新出现的多肽序列的蛋白质 - 蛋白质相互作用和新基序发现的结合位点预测。

DOI:
10.1186/1471-2105-12-225
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发表时间:
2011-06-02
期刊:
影响因子:
3
通讯作者:
Dehne F
Dehne F
中科院分区:
生物学4区
文献类型:
--
作者:
Amos-Binks A;Patulea C;Pitre S;Schoenrock A;Gui Y;Green JR;Golshani A;Dehne F

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虽然有许多方法可以预测蛋白质-蛋白质相互作用,但很少有方法可以确定每个蛋白质上相互作用的特定位点。介导相互作用的特定序列区域(结合位点)的表征对于理解细胞途径至关重要。由于实验的限制,实验方法经常报告错误的结合位点,而计算方法往往需要在蛋白质组规模上不可用的数据。在这里,我们提出了PIPE-Sites,一种基于重复出现的多肽序列对的蛋白质特异性结合位点预测的新方法,该方法先前已被证明可以准确地预测蛋白质-蛋白质相互作用。PIPE-Sites以高特异性运行,仅需要查询蛋白质的序列和已知二元相互作用的数据库,而不需要结合位点数据,使其适用于蛋白质组规模的结合位点预测。使用具有实验确定的结合位点的265个酵母和423个人类相互作用蛋白对的数据集来评估PIPE-Sites。我们发现,当应用于相同的数据集时,PIPE-Sites预测比现有的两种基于域-域相互作用的结合位点预测方法更接近确认的结合位点。最后,我们将PIPE-Sites应用于两个数据集,其中包括2347个酵母和14,438个人类新的相互作用蛋白对,这些蛋白对预测将以高置信度相互作用。预测的相互作用位点的分析揭示了一些蛋白质的重复性,这是高度重复发生在结合位点,这可能代表新的结合基序。PIPE-Sites是一种精确预测蛋白质结合位点的方法,适用于蛋白质组规模。因此,PIPE位点可以用于详尽分析整个蛋白质组中的蛋白质结合模式以及发现新的结合基序。PIPE-Sites可在http://pipe-sites.cgmlab.org/上获得。
While there are many methods for predicting protein-protein interaction, very few can determine the specific site of interaction on each protein. Characterization of the specific sequence regions mediating interaction (binding sites) is crucial for an understanding of cellular pathways. Experimental methods often report false binding sites due to experimental limitations, while computational methods tend to require data which is not available at the proteome-scale. Here we present PIPE-Sites, a novel method of protein specific binding site prediction based on pairs of re-occurring polypeptide sequences, which have been previously shown to accurately predict protein-protein interactions. PIPE-Sites operates at high specificity and requires only the sequences of query proteins and a database of known binary interactions with no binding site data, making it applicable to binding site prediction at the proteome-scale. PIPE-Sites was evaluated using a dataset of 265 yeast and 423 human interacting proteins pairs with experimentally-determined binding sites. We found that PIPE-Sites predictions were closer to the confirmed binding site than those of two existing binding site prediction methods based on domain-domain interactions, when applied to the same dataset. Finally, we applied PIPE-Sites to two datasets of 2347 yeast and 14,438 human novel interacting protein pairs predicted to interact with high confidence. An analysis of the predicted interaction sites revealed a number of protein subsequences which are highly re-occurring in binding sites and which may represent novel binding motifs. PIPE-Sites is an accurate method for predicting protein binding sites and is applicable to the proteome-scale. Thus, PIPE-Sites could be useful for exhaustive analysis of protein binding patterns in whole proteomes as well as discovery of novel binding motifs. PIPE-Sites is available online at http://pipe-sites.cgmlab.org/.
DOI: 10.1038/415141a
发表时间: 2002-01-10
期刊: NATURE
影响因子: 64.8
作者:
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发表时间: 2006-05-25
期刊: BMC BIOINFORMATICS
影响因子: 3
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