Assessing protein structures with a non-local atomic interaction energy
Assessing protein structures with a non-local atomic interaction energy
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DOI：
10.1006/jmbi.1998.1665
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发表时间：
1998-04-17
影响因子：
5.6
通讯作者：
Feytmans, E
中科院分区：
文献类型：
--
作者：
Melo, F;Feytmans, E
我们描述了一种基于非局部相互作用能的新方法来评估蛋白质结构。该方法使用一种非常灵敏和精确的原子平均力势（AMFP）来计算蛋白质结构的非局部能谱（NL - 谱）。对几个使用比较建模技术构建且包含若干错误的蛋白质模型进行了评估。这些模型呈现出良好的立体化学结构，并且之前已经用不同的、广泛使用的方法进行了检查，但这些方法未能检测出错误。由AMFP得出的能谱能够将高分与模型中的点错误和比对错误相关联。点错误经常出现在环区或模板与目标蛋白质之间结构差异的区域。比对错误能够以很高的分数被清晰地检测出来。该方法的性能也通过对X射线解析的蛋白质结构的评估进行了测试。在一个由143个解析良好且无冗余的蛋白质结构组成的数据集中，我们发现从AMFP获得的平均能量Z - 分数随着分辨率的降低而增加。对于那些已经被描述为具有异常立体化学结构的结构，会得到非常高的Z - 分数。此外，对一些过时的和替代的蛋白质对进行能量计算时，过时的蛋白质总是显示出更高的Z - 分数。最后，两个特殊案例显示了能谱在评估X射线解析的蛋白质结构中的有用性。首先，在错误的空间群中精修的蛋白质结构的NL - 谱在几个区域有非常高的分数。其中一个区域已经被描述为与该结构的密度图不匹配。在正确的空间群中重新精修的结构的NL - 谱有了极大的改善。在第二个案例中，该方法能够准确地指出无序残基，即使这些残基的原子没有违反范德华半径之和。用于计算包含一条或多条链的蛋白质结构的NL - 谱的程序ANOLEA可通过万维网访问：http://www.fundp.ac.be/pub/ANOLEA.html。（C）1998年学术出版社有限公司
We describe a new approach, based on the energy of non-local interactions, to assess protein structures. The method uses a very sensitive and accurate atomic mean force potential (AMFP) to calculate the nonlocal energy profile (NL-profile) of a proteins structure. Several protein models, built using the comparative modeling technique and containing several errors, were evaluated. These models exhibit a good stereochemistry and have been previously checked with different, widely used, methods that failed to detect the errors. The AMFP-derived energy profiles are able to correlate high scores with point errors and misalignments in the models. The point errors are frequently found in loops or regions of structural differences between the template and the target protein. The misalignments are clearly detected with very high scores.The performance of the method was also tested for the assessment of X-ray solved protein structures. Ln a data set of 143 well solved and non-redundant protein structures, we find that the average energy Z-scores, obtained from AMFP, increase as the resolution decreases. In the case of structures that have already been described as having an unusual stereochemistry, very high Z-scores are obtained. Moreover, energy calculations for some pairs of obsolete and replacement proteins always show higher Z-scores for the obsolete proteins. Finally, two particular cases show the usefulness of the profiles in the assessment of X-ray solved protein structures. First, the NL-profile of a protein structure refined in the incorrect space group has very high scores in several regions. One region-has already been described to be out-of-register with the density map of the structure. The NL-profile of the re-refined structure with the correct space group is vastly improved. In the second case, the method is able to accurately point out disordered residues, even if the atoms of these residues do not violate the sum of the van der Waals radii. ANOLEA, the program used to calculate the NL-profile of a protein structure containing one or more chains is accessible through the World Wide Web at: http://www.fundp.ac.be/pub/ANOLEA.html. (C) 1998 Academic Press Limited.