Secondary and tertiary structural effects on protein NMR chemical shifts: An ab initio approach

Recent theoretical developments permit the prediction of ¹H, ¹³C, ¹⁵N, and ¹⁹F nuclear magnetic resonance chemical shifts in proteins and offer new ways of analysing secondary and tertiary structure as well as for probing protein electrostatics. For ¹³C, φ,ψ torsion angles dominate shielding for Cα and Cβ, but the addition of hydrogen bonding and electrostatics gives even better accord with experiment. For ¹⁵N^H, side chain (χ¹) torsion angles are also important, as are nearest neighbor sequence effects, whereas for ¹H^N, hydrogen bonding is particularly significant. For ¹⁹F, weak or long-range electrostatic fields dominate ¹⁹F shielding nonequivalencies. The ability to predict chemical shifts in proteins from known or test structures opens new avenues to structure refinement or determination, especially for condensed systems.