Significant improvement in accuracy of multiple protein sequence alignments by iterative refinement as assessed by reference to structural alignments
Significant improvement in accuracy of multiple protein sequence alignments by iterative refinement as assessed by reference to structural alignments
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DOI：
10.1006/jmbi.1996.0679
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发表时间：
1996-12-13
影响因子：
5.6
通讯作者：
Gotoh, O
中科院分区：
文献类型：
--
作者：
Gotoh, O
通过参考54个独立家族的相应结构比对，评估了四种比对大量蛋白质序列的策略的相对性能。从已知结构及其同源物的序列中用给定的方法构建一个家族的多个序列比对，从整个比对中提取由已知结构的序列组成的子集，并以残基对残基的方式与结构对应物进行比较。针对每个家系和方法，优化了缺口开放和延伸惩罚。四种多重比对方法中的每一种都比传统的成对比对方法给出了明显更准确的比对。此外，在检查的四种多重比对方法中，有三种方法在性能上有明显的差异。目前最流行的渐进法在四种方法中排名最差，优化配对总和的随机迭代策略排名第二。两种表现最好的策略，其中一种是新开发的，都追求最优的加权配对总和得分，其中引入配对权重来校正家庭中子组的不均匀表示。新方法使用双重嵌套迭代来使比对、系统发育树和配对权重相互一致。最重要的是，与成对或渐进方法相比，这些迭代方法获得的比对精度的提高往往随着平均序列同一性的降低而增加，这意味着迭代精化对于通常困难的远程相关序列的比对更有效。四个著名的氨基酸替代矩阵也结合各种方法进行了测试。然而，在多重比对的框架中，替换矩阵的影响被发现是次要的，并且任何矩阵的比对方法的相对性能都观察到相同的数量级。(C)1996年学术出版社有限公司
The relative performances of four strategies for aligning a large number of protein sequences were assessed by referring to corresponding structural alignments of 54 independent families. Multiple sequence alignment of a family was constructed by a given method from the sequences of known structures and their homologues, and the subset consisting of the sequences of known structures was extracted from the whole alignment and compared with the structural counterpart in a residue-to-residue fashion. Gap-opening and -extension penalties were optimized for each family and method. Each of the four multiple alignment methods gave significantly more accurate alignments than the conventional pairwise method. In addition, a clear difference in performance was detected among three of the four multiple alignment methods examined. The currently most popular progressive method ranked worst among the four, and the randomized iterative strategy that optimizes the sum-of-pairs score ranked next worst. The two best-performing strategies, one of which was newly developed, both pursue an optimal weighted sum-of-pairs score, where the pair weights were introduced to correct for uneven representations of subgroups in a family. The new method uses doubly nested iterations to make alignment, phylogenetic tree and pair weights mutually consistent. Most importantly, the improvement in accuracy of alignments obtained by these iterative methods over pairwise or progressive method tends to increase with decreasing average sequence identity, implying that iterative refinement is more effective for the generally difficult alignment of remotely related sequences. Four well-known amino acid substitution matrices were also tested in combination with the various methods. However, the effects of substitution matrices were found to be minor in the framework of multiple alignment, and the same order of relative performance of the alignment methods was observed with any of the matrices. (C) 1996 Academic Press Limited