van den Akker F, Hol W G
Department of Biochemistry, University of Washington, Seattle, WA 98195-7420, USA.
Acta Crystallogr D Biol Crystallogr. 1999 Jan;55(Pt 1):206-18. doi: 10.1107/S0907444998007161. Epub 1999 Jan 1.
Methods for the evaluation of the accuracy of crystal structures of proteins and nucleic acids are of general importance for structure-function studies as well as for biotechnological and biomedical research based upon three-dimensional structures of biomacromolecules. The structure-validation program DDQ (difference-density quality) has been developed to complement existing validation procedures. The DDQ method is based on the information present in a difference electron-density map calculated with the water molecules deliberately omitted from the structure-factor calculation. The quality of a crystal structure is reflected in this difference map by (i) the height of solvent peaks occurring at physical chemically reasonable positions with respect to protein and ligand atoms and (ii) the number and height of positive and negative 'shift' peaks next to protein atoms. The higher the solvent peaks and the lower the shift peaks, the better the structure is likely to be. Moreover, extraneous positive density due to an incomplete molecular model is also monitored, since this is another indicator of imperfections in the structure. Automated analysis of these types of features in difference electron densities is used to quantify the local as well as global accuracy of a structure. In the case of proteins, the DDQ structure-validation method is found to be very sensitive to small local errors, to omitted atoms and also to global errors in crystal structure determinations.
评估蛋白质和核酸晶体结构准确性的方法对于结构功能研究以及基于生物大分子三维结构的生物技术和生物医学研究具有普遍重要性。已经开发了结构验证程序DDQ（差异密度质量）以补充现有的验证程序。DDQ方法基于在用结构因子计算中故意省略水分子的情况下计算出的差异电子密度图中存在的信息。晶体结构的质量在该差异图中通过以下方式反映：（i）相对于蛋白质和配体原子在物理化学合理位置出现的溶剂峰的高度，以及（ii）蛋白质原子旁边正、负“位移”峰的数量和高度。溶剂峰越高且位移峰越低，结构可能越好。此外，由于分子模型不完整而产生的无关正密度也受到监测，因为这是结构缺陷的另一个指标。对差异电子密度中这些类型特征的自动分析用于量化结构的局部以及整体准确性。在蛋白质的情况下，发现DDQ结构验证方法对小的局部误差、遗漏的原子以及晶体结构测定中的整体误差非常敏感。
