Positional Variance in NMR Crystallography

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.