The limit of accuracy of protein modeling: Influence of crystal packing on protein structure
The limit of accuracy of protein modeling: Influence of crystal packing on protein structure
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DOI：
10.1016/j.jmb.2005.05.066
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发表时间：
2005-08-12
影响因子：
5.6
通讯作者：
Sobolev, V
中科院分区：
文献类型：
--
作者：
Eyal, E;Gerzon, S;Sobolev, V
蛋白质数据库（PDB）的大小使得现在可以得出有关晶体堆积结构效应的统计结论。这些影响与设定蛋白质建模准确度的实际上限相关。将其晶体在不对称单元中具有多个分子或其结构至少两次通过X射线晶体学确定的蛋白质进行配对并分析它们的差异。我们证明了晶体环境对蛋白质结构的明显影响，包括主链构象、铰链状运动和侧链构象。表面水分子的位置在不同的晶体环境中往往会发生变化，而配体的位置则不然。由独立团体确定的结构比由同一作者确定的结构差异更大。使用不同的细化方法是这种效果的主要来源。我们的成对分析得出了蛋白质建模准确性的实际限制。对于不同的晶体形式，整个蛋白质的精度极限（C-α、均方根偏差 (RMSD)）类似于 0.8 埃，其中由于晶体堆积而导致的精度极限约为 0.3 埃。对于有组织的次级元素，C-α RMSD 的上限为 0.5-0.6 埃，而对于环或蛋白质表面，它达到 1.0 埃。百分之二十的暴露侧链表现出不同的 chi(1+2) 构象，其中大约一半的效应也是由晶体堆积造成的。可以使用基于网络的工具来分析和图形显示晶体接触的表面积（http://ligin.weizmann.ac.il/cryco）。 (c) 2005 Elsevier Ltd. 保留所有权利。
The size of the protein database (PDB) makes it now feasible to arrive at statistical conclusions regarding structural effects of crystal packing. These effects are relevant for setting upper practical limits of accuracy on protein modeling. Proteins whose crystals have more than one molecule in the asymmetric unit or whose structures were determined at least twice by X-ray crystallography were paired and their differences analyzed. We demonstrate a clear influence of crystal environment on protein structure, including backbone conformations, hinge-like motions and side-chain conformations. The positions of surface water molecules tend to be variable in different crystal environments while those of ligands are not. Structures determined by independent groups vary more than structures determined by the same authors. The use of different refinement methods is a major source for this effect. Our pair-wise analysis derives a practical limit to the accuracy of protein modeling. For different crystal forms, the limit of accuracy (C-alpha, root-mean-square deviation (RMSD)) is similar to 0.8 angstrom for the entire protein, which includes similar to 0.3 angstrom due to crystal packing. For organized secondary elements, the upper limit of C-alpha RMSD is 0.5-0.6 angstrom while for loops or protein surface it reaches 1.0 angstrom. Twenty percent of exposed side-chains exhibit different chi(1+2) conformations with approximately half of the effect also resulting from crystal packing. A web based tool for analysis and graphic presentation of surface areas of crystal contacts is available (http://ligin.weizmann.ac.il/cryco). (c) 2005 Elsevier Ltd. All rights reserved.