Ensemble refinement of protein crystal structures: Validation and application
Ensemble refinement of protein crystal structures: Validation and application
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DOI：
10.1016/j.str.2007.06.019
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发表时间：
2007-09-01
期刊：
影响因子：
5.7
通讯作者：
Phillips, George N., Jr.
中科院分区：
文献类型：
--
作者：
Levin, Elena J.;Kondrashov, Dmitry A.;Phillips, George N., Jr.
X射线晶体学通常使用单组坐标和B因子来描述大分子构象。对整个结构的多个副本进行细化以前曾在特定情况下用作表示结构灵活性的替代方法。在这里，我们系统地验证了这种方法，通过使用模拟的衍射数据，我们发现，系综细化产生更好的代表性的原子位置的分布在模拟的结构比单一构象细化。从改进的合奏和模拟计算的主成分的比较表明，一致的运动被捕获本地，但相关性消散在很长的距离。包围细化也用于50个不同分辨率的实验结构，并导致R-自由值的减少，这意味着改进的模拟结构观察到的灵活性的表示可能适用于真实的结构。这些增益基本上是独立的分辨率或数据参数比，这表明，即使在中等分辨率的结构可以受益于合奏细化。
X-ray crystallography typically uses a single set of coordinates and B factors to describe macromolecular conformations. Refinement of multiple copies of the entire structure has been previously used in specific cases as an alternative means of representing structural flexibility. Here, we systematically validate this method by using simulated diffraction data, and we find that ensemble refinement produces better representations of the distributions of atomic positions in the simulated structures than single-conformer refinements. Comparison of principal components calculated from the refined ensembles and simulations shows that concerted motions are captured locally, but that correlations dissipate over long distances. Ensemble refinement is also used on 50 experimental structures of varying resolution and leads to decreases in R-free values, implying that improvements in the representation of flexibility observed for the simulated structures may apply to real structures. These gains are essentially independent of resolution or data-to-parameter ratio, suggesting that even structures at moderate resolution can benefit from ensemble refinement.