International Center for Quantum and Molecular Structures, Shanghai University, Shanghai 200444, People's Republic of China.
Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic.
Acta Crystallogr D Struct Biol. 2020 Dec 1;76(Pt 12):1184-1191. doi: 10.1107/S2059798320013194. Epub 2020 Nov 19.
Electron cryo-microscopy (cryo-EM) is rapidly becoming a major competitor to X-ray crystallography, especially for large structures that are difficult or impossible to crystallize. While recent spectacular technological improvements have led to significantly higher resolution three-dimensional reconstructions, the average quality of cryo-EM maps is still at the low-resolution end of the range compared with crystallography. A long-standing challenge for atomic model refinement has been the production of stereochemically meaningful models for this resolution regime. Here, it is demonstrated that including accurate model geometry restraints derived from ab initio quantum-chemical calculations (HF-D3/6-31G) can improve the refinement of an example structure (chain A of PDB entry 3j63). The robustness of the procedure is tested for additional structures with up to 7000 atoms (PDB entry 3a5x and chain C of PDB entry 5fn5) using the less expensive semi-empirical (GFN1-xTB) model. The necessary algorithms enabling real-space quantum refinement have been implemented in the latest version of qr.refine and are described here.
电子冷冻显微镜（cryo-EM）技术正在迅速成为 X 射线晶体学的主要竞争对手，特别是对于那些难以或不可能结晶的大型结构。虽然最近的技术进步取得了令人瞩目的成果，实现了更高分辨率的三维重构，但与晶体学相比，冷冻电镜图谱的平均质量仍处于低分辨率范围。长期以来，原子模型精修的一个挑战是针对该分辨率范围生成具有合理立体化学的模型。在这里，证明了包含源自从头算量子化学计算（HF-D3/6-31G）的准确模型几何限制可以改进示例结构（PDB 条目 3j63 中的链 A）的精修。该程序的稳健性已使用更便宜的半经验（GFN1-xTB）模型针对多达 7000 个原子的其他结构（PDB 条目 3a5x 和 PDB 条目 5fn5 的链 C）进行了测试。能够进行实空间量子精修的必要算法已在最新版本的 qr.refine 中实现，并在此处进行了描述。
