Levin Elena J, Kondrashov Dmitry A, Wesenberg Gary E, Phillips George N
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Structure. 2007 Sep;15(9):1040-52. doi: 10.1016/j.str.2007.06.019.
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.
X射线晶体学通常使用一组坐标和B因子来描述大分子构象。此前在特定情况下，已采用对整个结构的多个副本进行精修作为表示结构灵活性的另一种方法。在这里，我们通过使用模拟衍射数据系统地验证了该方法，并且我们发现，与单构象精修相比，系综精修能更好地表示模拟结构中原子位置的分布。对从精修系综和模拟中计算出的主成分进行比较表明，协同运动在局部被捕获，但相关性在长距离上会消散。系综精修还应用于50个不同分辨率的实验结构，并导致R（自由）值降低，这意味着在模拟结构中观察到的灵活性表示的改善可能适用于真实结构。这些收益基本上与分辨率或数据与参数的比率无关，这表明即使是中等分辨率的结构也可以从系综精修中受益。
