ACCURATE MODELING OF PROTEIN CONFORMATION BY AUTOMATIC SEGMENT MATCHING
ACCURATE MODELING OF PROTEIN CONFORMATION BY AUTOMATIC SEGMENT MATCHING
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DOI：
10.1016/0022-2836(92)90964-l
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发表时间：
1992-07-20
影响因子：
5.6
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
LEVITT, M
片段匹配建模使用高度精确的已知蛋白质X射线结构的数据库，根据其氨基酸序列和少数原子（通常仅C α原子）的原子坐标构建未知的靶结构。首先将目标结构分解为一组短段。然后在数据库中搜索匹配的片段，这些片段被拟合到目标结构的框架上。三个标准用于选择匹配的数据库片段：氨基酸序列相似性、构象相似性（原子坐标）和与靶结构的相容性（货车范德华相互作用）。新方法的效果令人惊讶：对于8个大小从46到323个残基的测试蛋白质，建模结构的全原子均方根偏差在0.93 μ m到1.73 μ m之间（平均值为1.26 μ m）。这个幅度的偏差是与那些发现的蛋白质的坐标之前和之后，对X-射线数据或坐标的相同的蛋白质在不同的晶体包装细化。这些结果对C α位置的误差或缺失的C α原子不敏感：精确的模型可以在C α误差高达1 μ s或仅使用一半的C α原子的情况下建立。通过基于不同的随机选择建立几个独立的模型，然后对坐标进行平均，可以显着提高对X射线结构的拟合;这种新概念对其他建模任务具有普遍意义。段匹配建模方法是全自动的，在没有任何人为干预的情况下产生一组完整的原子坐标，并且是有效的（在Silicon Graphics 4 D 25 Personal Iris工作站上为14秒/残基）。
Segment match modeling uses a data base of highly refined known protein X-ray structures to build an unknown target structure from its amino acid sequence and the atomic co-ordinates of a few of its atoms (generally only the C α atoms). The target structure is first broken into a set of short segments. The data base is then searched for matching segments, which are fitted onto the framework of the target structure. Three criteria are used for choosing a matching data base segment: amino acid sequence similarity, conformational similarity (atomic co-ordinates), and compatibility with the target structure (van der Waals' interactions). The new method works surprisingly well: for eight test proteins ranging in size from 46 to 323 residues, the all-atom root-mean-square deviation of the modeled structures is between 0· 93 Å and 1· 73 Å (the average is 1· 26 Å). Deviations of this magnitude are comparable with those found for protein co-ordinates before and after refinement against X-ray data or for co-ordinates of the same protein in different crystal packings. These results are insensitive to errors in the C α positions or to missing C α atoms: accurate models can be built with C α errors of up to 1 Å or by using only half the C α atoms. The fit to the X-ray structures is improved significantly by building several independent models based on different random choices and then averaging co-ordinates; this novel concept has general implications for other modeling tasks. The segment match modeling method is fully automatic, yields a complete set of atomic co-ordinates without any human intervention and is efficient (14s/residue on the Silicon Graphics 4 D 25 Personal Iris workstation).