High-resolution structure prediction and the crystallographic phase problem.
High-resolution structure prediction and the crystallographic phase problem.
复制标题
高分辨率结构预测和晶体学期问题。
DOI：
10.1038/nature06249
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发表时间：
2007-11-08
期刊：
影响因子：
64.8
通讯作者：
Baker, David
中科院分区：
文献类型：
--
作者：
Qian, Bin;Raman, Srivatsan;Das, Rhiju;Bradley, Philip;McCoy, Airlie J;Read, Randy J;Baker, David
我们描述了一种改进蛋白质结构模型的新方法，该方法将采样集中在最可能包含错误的区域，同时允许整个结构在物理上真实的全原子力场中放松。在使用核磁共振数据生成的模型和基于远端结构同源物的比较模型的应用中，该方法可以显着提高结构在主结构和核心侧链位置方面的准确性。此外，所得到的模型满足了一项特别严格的测试：它们为分子替代试验中的x射线晶体学相问题提供了明显更好的解决方案。最后，我们证明了全原子精化可以产生新的蛋白质结构预测，达到分子替代所需的高精度。在没有任何实验相信息的情况下，在没有任何适合于蛋白质数据库中分子替换的模板的情况下，确定了一个112残基蛋白的衍射数据的相。这些结果表明，高分辨率结构预测与最先进的相位工具的结合可能在相位晶体学数据中出乎意料地强大，因为分子替换由于缺乏足够精确的先前模型而受到阻碍。
We describe a new approach to refining protein structure models that focuses sampling in regions most likely to contain errors while allowing the whole structure to relax in a physically realistic all-atom force field. In applications to models produced using NMR data and to comparative models based on distant structural homologues, the method can significantly improve the accuracy of the structures in terms of both the backbone conformations and the placement of core side chains. Further, the resulting models satisfy a particularly stringent test: they provide significantly better solutions to the X-ray crystallographic phase problem in molecular replacement trials. Finally, we show that all-atom refinement can produce de novo protein structure predictions that reach the high accuracy required for molecular replacement. Phases for diffraction data for a 112-residue protein have been determined without any experimental phase information and in the absence of any templates suitable for molecular replacement from the Protein Data Bank. These results suggest that the combination of high resolution structure prediction with state-of-the-art phasing tools may be unexpectedly powerful in phasing crystallographic data for which molecular replacement is hindered by the absence of sufficiently accurate prior models.