Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
J Am Chem Soc. 2017 Feb 22;139(7):2573-2576. doi: 10.1021/jacs.6b12705. Epub 2017 Feb 8.
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.
我们提出了一种方法来量化通过基于化学位移的 NMR 晶体学确定的晶体结构中的位置不确定性。该方法将分子动力学模拟和密度泛函理论计算与实验和计算化学位移不确定性相结合。通过这种方式，我们找到了由 NMR 晶体学确定的晶体结构中每个原子的平均位置精度以及各向同性和各向异性位置精度。该方法在可卡因、氟他胺、氟灭酸、青霉素 G 的 K 盐和药物 4-[4-(2-金刚烷基氨基甲酰基)-5-叔丁基吡唑-1-基]苯甲酸（AZD8329）的形式 4 的晶体结构上进行了演示。我们发现，对于可卡因的晶体结构，不确定性对应于 0.17Å 的位置 RMSD。这比基于单晶 X 射线衍射的结构确定的不确定性小 2.5 倍。
