The ConSurf-HSSP database: The mapping of evolutionary conservation among homologs onto PDB structures
The ConSurf-HSSP database: The mapping of evolutionary conservation among homologs onto PDB structures
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DOI：
10.1002/prot.20305
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发表时间：
2005-02-15
影响因子：
2.9
通讯作者：
Ben-Tal, N
中科院分区：
文献类型：
--
作者：
Glaser, F;Rosenberg, Y;Ben-Tal, N
HSSP(同源衍生蛋白质二级结构)数据库提供蛋白质数据库(PDB)中已知三维(3D)结构蛋白质的多序列比对(MSA)。该数据库还包含对每个氨基酸位置的进化保守程度的估计。这一基于相对熵的估计与位置的功能重要性相关；进化上保守的位置(即变异性有限、熵低的位置)有时对于维持蛋白质的三维结构和生物功能很重要(S)。我们最近开发了Rate4Site算法，用于根据计算的进化速度对氨基酸保守性进行评分。该算法考虑了同源基因之间的系统发育关系和进化过程的随机性。在这里，我们提供了ConSurf-HSSP数据库的Rate4Site估计的氨基酸位置的进化速率，使用HSSP的MSA计算。该数据库提供了几乎所有PDB的预先计算的进展率。这些比率使用色码投影到蛋白质结构上，并可以使用CON-Surf服务器界面在线查看。为了举例说明数据库，我们详细地分析了丙酮酸激酶的保守模式，并将结果与使用HSSP数据库的相对熵分数观察到的结果进行了比较。令人欣慰的是，使用这两个保守分数都可以检测到该酶的主要功能区。有趣的是，ConSurf-HSSP的计算绘制了额外的功能重要区域，这些区域是适度保守的，被原始的HSSP估计忽略了。可在线获得ConSurf-HSSP数据库(http://consurf-hssp.tau.ac.il).(C)2004年Wiley-Liss，Inc.
The HSSP (Homology-Derived Secondary Structure of Proteins) database provides multiple sequence alignments (MSAs) for proteins of known three-dimensional (3D) structure in the Protein Data Bank (PDB). The database also contains an estimate of the degree of evolutionary conservation at each amino acid position. This estimate, which is based on the relative entropy, correlates with the functional importance of the position; evolutionarily conserved positions (i.e., positions with limited variability and low entropy) are occasionally important to maintain the 3D structure and biological function(s) of the protein. We recently developed the Rate4Site algorithm for scoring amino acid conservation based on their calculated evolutionary rate. This algorithm takes into account the phylogenetic relationships between the homologs and the stochastic nature of the evolutionary process. Here we present the ConSurf-HSSP database of Rate4Site estimates of the evolutionary rates of the amino acid positions, calculated using HSSP's MSAs. The database provides precalculated evolutionary rates for nearly all of the PDB. These rates are projected, using a color code, onto the protein structure, and can be viewed online using the Con-Surf server interface. To exemplify the database, we analyzed in detail the conservation pattern obtained for pyruvate kinase and compared the results with those observed using the relative entropy scores of the HSSP database. It is reassuring to know that the main functional region of the enzyme is detectable using both conservation scores. Interestingly, the ConSurf-HSSP calculations mapped additional functionally important regions, which are moderately conserved and were overlooked by the original HSSP estimate. The ConSurf-HSSP data-base is available online (http://consurf-hssp.tau.ac.il). (C) 2004Wiley-Liss, Inc.