Clabbers Max T B, Gruene Tim, van Genderen Eric, Abrahams Jan Pieter
Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Paul Scherrer Institut (PSI), CH-5232 Villigen PSI, Switzerland.
Acta Crystallogr A Found Adv. 2019 Jan 1;75(Pt 1):82-93. doi: 10.1107/S2053273318013918.
Compared with X-rays, electron diffraction faces a crucial challenge: dynamical electron scattering compromises structure solution and its effects can only be modelled in specific cases. Dynamical scattering can be reduced experimentally by decreasing crystal size but not without a penalty, as it also reduces the overall diffracted intensity. In this article it is shown that nanometre-sized crystals from organic pharmaceuticals allow positional refinement of the hydrogen atoms, even whilst ignoring the effects of dynamical scattering during refinement. To boost the very weak diffraction data, a highly sensitive hybrid pixel detector was employed. A general likelihood-based computational approach was also introduced for further reducing the adverse effects of dynamic scattering, which significantly improved model accuracy, even for protein crystal data at substantially lower resolution.
与X射线相比，电子衍射面临一个关键挑战：动态电子散射会影响结构解析，其效应只能在特定情况下进行建模。通过减小晶体尺寸可以在实验上减少动态散射，但这并非没有代价，因为这也会降低整体衍射强度。本文表明，来自有机药物的纳米级晶体即使在精修过程中忽略动态散射的影响，也能对氢原子进行位置精修。为了增强非常微弱的衍射数据，采用了高灵敏度的混合像素探测器。还引入了一种基于一般似然性的计算方法，以进一步减少动态散射的不利影响，这显著提高了模型精度，即使对于分辨率低得多的蛋白质晶体数据也是如此。
