J Am Chem Soc. 2017 Feb 22;139(7):2573-2576. doi: 10.1021/jacs.6b12705. Epub 2017 Feb 08.
Journal of the American Chemical Society
Albert Hofstetter, Lyndon Emsley
PMID: 28146348 DOI: 10.1021/jacs.6b12705
We propose a method to quantify positional uncertainties in crystal structures determined by chemical-shift-based NMR crystallography. The method combines molecular dynamics simulations and density functional theory calculations with experimental and computational chemical shift uncertainties. In this manner we find the average positional accuracy as well as the isotropic and anisotropic positional accuracy associated with each atom in a crystal structure determined by NMR crystallography. The approach is demonstrated on the crystal structures of cocaine, flutamide, flufenamic acid, the K salt of penicillin G, and form 4 of the drug 4-[4-(2-adamantylcarbamoyl)-5-tert-butylpyrazol-1-yl]benzoic acid (AZD8329). We find that, for the crystal structure of cocaine, the uncertainty corresponds to a positional RMSD of 0.17 Å. This is a factor of 2.5 less than for single-crystal X-ray-diffraction-based structure determination.
