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首页> 外文会议>Symposium on Structures and Mechanisms: from Ashes to Enzymes, May 12-14, 2000 >Scoring Functions Sensitive to Alignment Error Have a More Difficult Search: A Paradox for Threading
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Scoring Functions Sensitive to Alignment Error Have a More Difficult Search: A Paradox for Threading

机译：对对齐错误敏感的评分函数进行更困难的搜索：线程悖论

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The task of recognizing protein sequence-structure compatibility (or threading) holds promise for detecting similarities that can not be seen with sequence analysis alone. The development of a method that can recognize a fold as well as the correct correspondence (or alignment) to the sequence remains a major challenge. We have created a new threading evaluation function that (1) uses a full atomic representation of structure (rapidly instantiating a plausible set of sidechains), (2) reflects the idiosyncrasies of particular environments within a fold family, and (3) is very sensitive to shifts away from the correct alignment. We illustrate these characteristics in the context of the globin family. We created a statistical model of globin environments using a structural alignment of 13 globin (and globin-like) molecules. We tested these with cross-validation, and found that our method reliably recognizes the correct alignments with sequence identities in the range of 11% to 18% identity, as long as the backbone upon which the sequence is threaded (the template backbone) is within 2.9 A RMSD of the actual backbone. When the backbone is more than 3.0 A from the template backbone, we are unable to detect the correct alignment. Our method shows sensitivity to both systematic and random shifts in the alignment―even with shifts of a single residue. These results suggest that threading methods using atomic detail and statistical descriptions of structural environments can be effective. Such methods, however, make the search for sequence-structure compatibility more difficult, since they create narrow, steep optima.
机译：识别蛋白质序列结构兼容性（或线程连接）的任务有望用于检测仅通过序列分析无法发现的相似性。能够识别折叠以及与序列正确对应（或比对）的方法的开发仍然是主要挑战。我们创建了一个新的线程评估函数，该函数（1）使用结构的完整原子表示（快速实例化一组合理的侧链），（2）反映折叠族内特定环境的特质，并且（3）非常敏感偏离正确的对齐方式。我们在球蛋白家族的背景下说明了这些特征。我们使用13个球蛋白（和球蛋白样）分子的结构比对创建了球蛋白环境的统计模型。我们通过交叉验证对这些序列进行了测试，发现只要序列所连接的主链（模板主链）在该主链内（模板主链），则我们的方法可以可靠地识别序列比对范围为11％至18％的正确比对2.9实际骨干的RMSD。当主干距离模板主干超过3.0 A时，我们将无法检测到正确的对齐方式。我们的方法显示出对比对中系统和随机移位的敏感性，即使是单个残基的移位也是如此。这些结果表明，使用原子详细信息和结构环境的统计描述进行穿线方法可能是有效的。但是，由于这些方法会产生狭窄，陡峭的最优值，因此使搜索序列结构兼容性变得更加困难。

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