A novel method for protein-protein interaction site prediction using phylogenetic substitution models.
A novel method for protein-protein interaction site prediction using phylogenetic substitution models.
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DOI：
10.1002/prot.23169
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发表时间：
2012-01
影响因子：
2.9
通讯作者：
Kihara, Daisuke
中科院分区：
文献类型：
--
作者：
La, David;Kihara, Daisuke
关键词：
蛋白质-蛋白质结合事件介导细胞中许多关键的生物学功能。通常，通过考虑序列保守性可以很好地识别蛋白质中功能重要的位点。然而，蛋白质-蛋白质相互作用位点比其他功能区域（例如酶的催化位点）表现出更高的序列变异。因此，导致序列保守性较弱的突变行为对蛋白质-蛋白质相互作用位点预测提出了重大挑战。在这里，我们提出了一个系统发育框架来捕获关键序列变异，这些变异有利于选择蛋白质-蛋白质结合所必需的残基。通过对不同蛋白质家族的综合分析，我们发现与其他表面残基相比，蛋白质结合界面表现出独特的氨基酸取代。基于此分析，我们开发了一种新方法 BindML，它利用替换模型来预测具有未知相互作用伙伴的蛋白质的蛋白质-蛋白质结合位点。 BindML 估计查询蛋白质结构中局部表面区域的系统发育树遵循蛋白质结合界面和非结合表面的替换模式的可能性。与蛋白质结合界面预测的替代方法相比，BindML 表现良好。本研究开发的方法非常通用，可以普遍应用于预测其他类型的功能位点，例如蛋白质中的 DNA、RNA 和膜结合位点。
Protein-protein binding events mediate many critical biological functions in the cell. Typically, functionally important sites in proteins can be well identified by considering sequence conservation. However, protein-protein interaction sites exhibit higher sequence variation than other functional regions, such as catalytic sites of enzymes. Consequently, the mutational behavior leading to weak sequence conservation poses significant challenges to the protein-protein interaction site prediction. Here, we present a phylogenetic framework to capture critical sequence variations that favor the selection of residues essential for protein-protein binding. Through the comprehensive analysis of diverse protein families, we show that protein binding interfaces exhibit distinct amino acid substitution as compared with other surface residues. Based on this analysis, we have developed a novel method, BindML, which utilizes the substitution models to predict protein-protein binding sites of protein with unknown interacting partners. BindML estimates the likelihood that a phylogenetic tree of a local surface region in a query protein structure follows the substitution patterns of protein binding interface and non-binding surfaces. BindML is shown to perform well compared to alternative methods for protein binding interface prediction. The methodology developed in this study is very versatile in the sense that it can be generally applied for predicting other types of functional sites, such as DNA, RNA, and membrane binding sites in proteins.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
DOI：
10.1016/s0097-8485(96)80004-0
发表时间：
1996-03-01
期刊：
COMPUTERS & CHEMISTRY
影响因子：
--
作者：
Gribskov, M;Robinson, NL
通讯作者：
Robinson, NL
影响因子：
3
作者：
通讯作者：
--
影响因子：
13.8
作者：
Henrick, K;Thornton, JM
通讯作者：
Thornton, JM
影响因子：
3.9
作者：
Arvestad, Lars
通讯作者：
Arvestad, Lars