Three-dimensional cluster analysis identifies interfaces and functional residue clusters in proteins
Three-dimensional cluster analysis identifies interfaces and functional residue clusters in proteins
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DOI：
10.1006/jmbi.2001.4540
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发表时间：
2001-04-13
影响因子：
5.6
通讯作者：
Eisenberg, D
中科院分区：
文献类型：
--
作者：
Landgraf, R;Xenarios, I;Eisenberg, D
三维聚类分析提供了一种预测蛋白质中功能残基簇的方法。该方法需要代表性结构和多序列比对作为输入数据。单个残基以区域比对表示，区域比对反映了它们的结构环境和它们的进化变异，如通过同源序列的比对所定义的。从整体（全球）和残基特异性（区域）的比对，我们计算全球和区域的相似性矩阵，包含在各自的比对中的所有成对序列比较的分数。比较矩阵，每个残基得到两个分数。区域保守性得分（C-R（x））定义了每个残基x及其邻居在3D空间中相对于整个蛋白质的保守性。相似性偏差得分（S（x））检测具有偏离全长序列所暗示的相似性的序列相似性的残基簇。我们评估了一组35个家庭的蛋白质与可用的共晶结构的三维聚类分析，显示小配体接口，核酸接口和两种类型的蛋白质-蛋白质接口（瞬时和稳定）。我们详细介绍了两个例子：果糖-1，6-二磷酸醛缩酶和丝裂原活化蛋白激酶ERK 2。我们发现，区域保护分数（C-R（x））识别功能性残基簇比不考虑3D信息的评分方案更好。C-R（x）对于预测保守性差的瞬时蛋白质-蛋白质界面特别有用。许多研究的蛋白质含有残基簇与升高的相似性偏差分数。这些残基簇与特异性赋予区域相关：因此，3D聚类分析代表了一种易于应用的方法，用于预测蛋白质中残基的功能相关空间簇。(C)北京：科学出版社.
Three-dimensional cluster analysis offers a method for the prediction of functional residue clusters in proteins. This method requires a representative structure and a multiple sequence alignment as input data. Individual residues are represented in terms of regional alignments that reflect both their structural environment and their evolutionary variation, as defined by the alignment of homologous sequences. From the overall (global) and the residue-specific (regional) alignments, we calculate the global and regional similarity matrices, containing scores for all pairwise sequence comparisons in the respective alignments. Comparing the matrices yields two scores for each residue. The regional conservation score (C-R(x)) defines the conservation of each residue x and its neighbors in 3D space relative to the protein as a whole. The similarity deviation score (S(x)) detects residue clusters with sequence similarities that deviate from the similarities suggested by the full-length sequences. We evaluated 3D cluster analysis on a set of 35 families of proteins with available cocrystal structures, showing small ligand interfaces, nucleic acid interfaces and two types of protein-protein interfaces (transient and stable). We present two examples in detail: fructose-1,6-bisphosphate aldolase and the mitogen-activated protein kinase ERK2. We found that the regional conservation score (C-R(x)) identifies functional residue clusters better than a scoring scheme that does not take 3D information into account. C-R(x) is particularly useful for the prediction of poorly conserved, transient protein-protein interfaces. Many of the proteins studied contained residue clusters with elevated similarity deviation scores. These residue clusters correlate with specificity-conferring regions: 3D cluster analysis therefore represents an easily applied method for the prediction of functionally relevant spatial clusters of residues in proteins. (C) 2001 Academic Press.