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.
Electron cryo-microscopy (cryo-EM) is fast becoming a major competitor to X-ray crystallography especially for large structures that are difficult or impossible to crystallize. While recent spectacular technology improvements are leading to significantly higher resolution of three-dimensional reconstructions, the average quality of cryo-EM maps is still on the low-resolution end of the range compared to crystallography. A long-standing challenge for atomic model refinement has been the production of stereochemically meaningful models for this resolution regime. Here we demonstrate how including accurate model geometry restraints derived from ab initio quantum-chemical calculations (HF-D3/6-31G) can improve the refinements of an example structure (chain A of 3j63). The robustness of the procedure is tested for additional structures with up to 7k atoms (3a5x, and chain C of 5fn5) by means of the less expensive semi-empirical (GFN1-xTB) model. Necessary algorithms enabling real-space quantum refinement are implemented in the latest version of qr.refine and are described herein.SynopsisThe implementation of quantum-based real-space refinement in qr.refine is described.
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