The structural alignment between two proteins: Is there a unique answer?
The structural alignment between two proteins: Is there a unique answer?
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DOI：
10.1002/pro.5560050711
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发表时间：
1996-07-01
期刊：
影响因子：
8
通讯作者：
Godzik, A
中科院分区：
文献类型：
--
作者：
Godzik, A
许多研究人员使用各种结构比较工具发现并重新发现了结构相似的BUR顺序无关的蛋白质。对于几对这样的蛋白质，从文献中获得的现有结构比对以及使用几个不同的相似性标准制备的比对被相互比较。结果表明，它们总体上是不同的，差异随着序列相似性的减小而增大。在优化全局相似性度量(例如Cα原子之间的均方根偏差)的比对与关注更局部特征的比对(例如包装或相互作用模式相似性)之间的差异尤其明显。简单地说，通过强调结构的不同方面，不同的结构对齐以不同的方式显示了毋庸置疑的相似性。由于不同路线之间的差异延伸到它们在所有位置都可能不同的点，对结构相似性的分析导致了使用不同的路线技术的小组报告的相互矛盾的结果。结果表明，对齐通常是退化的，并且整族对齐可以生成几乎与最优对齐相同的分数。然而，对于一些相似性标准，特别是那些基于侧链位置而不是Cα位置的标准，蛋白质某些区域的比对是唯一的。这打开了一个问题，即结构比对如何以及是否可以用作蛋白质比较的“真理标准”。
Structurally similar bur sequentially unrelated proteins have been discovered and rediscovered by many re searchers, using a variety of structure comparison tools. For several pairs of such proteins, existing structural alignments obtained from the literature, as well as alignments prepared using several different similarity criteria, are compared with each other. It is shown that, in general, they differ from each other, with differences increasing with diminishing sequence similarity. Differences are particularly strong between alignments optimizing global similarity measures, such as RMS deviation between C alpha atoms, and alignments focusing on more local features, such as packing or interaction pattern similarity. Simply speaking, by putting emphasis on different aspects of structure, different structural alignments show the unquestionable similarity in a different way. With differences between various alignments extending to a point where they can differ at all positions, analysis of structural similarities leads to contradictory results reported by groups using different alignment techniques.The problem of uniqueness and stability of structural alignments is further studied with the help of visualization of the suboptimal alignments. It is shown that alignments are often degenerate and whole families of align ments can be generated with almost the same score as the ''optimal alignment.'' However, for some similarity criteria, specially those based on side-chain positions, rather than C alpha positions, alignments in some areas of the protein are unique. This opens the question of how and if the structural alignments can be used as ''standards of truth'' for protein comparison.