A new model for chemical shifts of amide hydrogens in proteins.

We propose a new computational model to predict amide proton chemical shifts in proteins. In addition to the ring-current, susceptibility and electrostatic effects of earlier models, we add a hydrogen-bonding term based on density functional calculations of model peptide-peptide and peptide-water systems. Both distance and angular terms are included, and the results are rationalized in terms of natural bond orbital analysis of the interactions. Comparison to observed shifts for 15 proteins shows a significant improvement over existing structure-shift correlations. These additions are incorporated in a new version of the SHIFTS program.