AUTOMATIC-ANALYSIS OF PROTEIN CONFORMATIONAL-CHANGES BY MULTIPLE LINKAGE CLUSTERING
AUTOMATIC-ANALYSIS OF PROTEIN CONFORMATIONAL-CHANGES BY MULTIPLE LINKAGE CLUSTERING
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DOI：
10.1006/jmbi.1995.0578
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发表时间：
1995-11-03
影响因子：
5.6
通讯作者：
WODAK, SJ
中科院分区：
文献类型：
--
作者：
BOUTONNET, NS;ROOMAN, MJ;WODAK, SJ
提出了一种用于分析蛋白质构象变化的自动算法，例如在底物结合或相同蛋白质的不同晶体形式中发生的构象变化。使用，作为唯一的信息，一个公平的蛋白质结构的原子坐标，该程序首先生成结构比对，优化的均方根偏差的骨干原子。为此，等价的二级结构和/或环从两种蛋白质相结合的多重链接层次聚类算法，它产生几个交织的聚类树。自动分析这些聚类树是用来剖析的构象变化的机制。它允许识别静态核心，代表不经历结构变化的二级结构的集合，以及其他像刚体一样移动的实体。它还允许描述二级结构或环相对于该核心或实体的运动。使用该信息，可以推断特定构象变化是否涉及剪切或铰链运动，或两者的组分。该算法被施加到柠檬酸合酶，乳酸脱氢酶，乳铁蛋白和β-葡糖基转移酶的构象变化的分析，代表剪切和铰链型机制的典型例子，和不同的运动尺寸范围。结果表明，与以前的分析非常一致，并提供额外的信息，给出了一个更完整和客观的图片的构象变化。使用我们的自动算法，我们发现，任何构象变化可以被视为具有剪切和铰链型运动的组件。确定哪一个是最合适的，需要结合我们的程序提供的信息与蛋白质三级结构的详细知识。(C)1995年学术出版社
An automatic algorithm is presented for analyzing protein conformational changes such as those occurring upon substrate binding or in different crystal forms of the same protein. Using, as sole information, the atomic coordinates of a Fair of protein structures, the procedure first generates structure alignments, which optimize the root-mean-square deviation of the backbone atoms. To this end, equivalent secondary structures and/or loops from both proteins are combined by a multiple linkage hierarchic clustering algorithm, which generates several intertwined clustering trees. Automatic analysis of these clustering trees is used to dissect the mechanism of the conformational change. It allows the identification of the static core, representing the collection of secondary structures which undergo no structural changes, as well as other entities which move like rigid bodies. It also permits the description of the movement of secondary structures or loops relative to this core or entities. Using this information, it can be inferred whether a particular conformational change involves shear or hinge motion, or components of both. The algorithm is applied to the analysis of the conformational changes of citrate synthase, lactate dehydrogenase, lactoferrin and beta-glucosyltransferase, representing typical examples of shear- and hinge-type mechanisms, and a varied range in movement size. The results are shown to be in excellent agreement with previous analyses, and to provide additional information which gives a more complete and objective picture of the conformational change. Using our automatic algorithm, we find that any conformational change may be viewed as having components of both shear- and hinge-type motion. Determining which of these is most appropriate requires the combination of the information provided by our procedure with detailed knowledge of the protein tertiary structures. (C) 1995 Academic Press Limited