Analysis of proton chemical shifts in regular secondary structure of proteins

Summary

The contribution of peptide groups to H^α and H^β proton chemical shifts can be modeled with empirical equations that represent magnetic anisotropy and electrostatic interactions [Ösapay, K. and Case, D.A. (1991) J. Am. Chem. Soc., 113, 9436–9444]. Using these, a model for the ‘random coil’ reference state can be generated by averaging a dipeptide over energetically allowed regions of torsion-angle space. Such calculations support the notion that the empirical constant used in earlier studies arises from neighboring peptide contributions in the reference state, and suggest that special values be used for glycine and proline residues, which differ significantly from other residues in their allowed ϕ,ψ-ranges. New constants for these residues are reported that provide significant improvements in predicted backbone shifts. To illustrate how secondary structure affects backbone chemical shifts we report calculations on oligopeptide models for helices, sheets and turns. In addition to suggesting a physical mechanism for the widely recognized average difference between α and β secondary structures, these models suggest several additional regularities that should be expected: (a) H^α protons at the edges of β-sheets will have a two-residue periodicity; (b) the H^α2 and H^α3 protons of glycine residues will exhibit different shifts, particularly in sheets; (c) H^β protons will also be sensitive to local secondary structure, but in different directions and to a smaller extent than H^α protons; (d) H^α protons in turns will generally be shifted upfield, except those in position 3 of type I turns. Examples of observed shift patterns in several proteins illustrate the application of these ideas.