Predicting N-15 amide chemical shifts in proteins. I. An additive model for the backbone contribution

Because proteins adopt unique structures, chemically identical nuclei in pr oteins exhibit different chemical shifts. Amide N-15 chemical shifts have b een shown to vary over 20 ppm. The cause of these chemical shift inequivale ncies is the different intra- and intermolecular interactions that individu al nuclei experience at different locations in the protein structure. These chemical shift inequivalencies can be described as structural shifts, the difference between the actual chemical shift and the random coil chemical s hift. As a first step toward the prediction of these amide N-15 structural shifts, calculations have been carried out on acetyl-glycine-methyl amide t o examine how a neighboring peptide group influences the amide N-15 structu ral shifts. The phi, psi dihedral angle space is completely surveyed, while all other geometrical variables are held fixed, to isolate the Effect of t he backbone conformation. Similar calculations for a limited number of conf ormations of acetyl-glycine-glycine-methyl amide were carried out, where th e effects of the two terminal peptide groups on the central amide N-15 stru ctural shift are examined. It is shown that the effect of the two adjacent groups can be accurately modeled by combining their individual effects addi tively. This provides a quite simple method to predict the backbone influen ce on amide N-15 structural shifts in proteins. (C) 2001 John Wiley & Sons, Inc.