Secondary structural effects on protein NMR chemical shifts.

For an amino acid in protein, its chemical shift, delta(phi, psi)(s), is expressed as a function of its backbone torsion angles (phi and psi) and secondary state (s): delta(phi, psi)(s=deltaphi, psi)_coil+Deltadelta(phi, psi)_s), where delta(phi, psi)(coil) represents its chemical shift at coil state (s=coil); Delta delta(phi, psi)(s) (s=sheet or helix) is herein defined as secondary structural effect correction factor, which are quantitatively determined from Residue-specific Secondary Structure Shielding Surface (RSS) for (13)CO, (13)Calpha, (13)Cbeta,(1)Halpha, (15)N, and (1)HN nuclei. The secondary structural effect correction factors defined in this study differ from those in earlier investigations by separating out the backbone conformational effects. As a consequence, their magnitudes are significantly smaller than those earlier reported. The present Delta delta(phi, psi)(sheet) and Delta delta(phi, psi)(helix) were found varying little with backbone conformation and the 20 amino acids, specifically for (13)CO, (13)Calpha, and (1)Halpha nuclei. This study also carries out some useful investigations on other chemical shift prediction approaches - the traditional shielding surfaces, SHIFTS, SHIFTX, PROSHIFT, and identifies some unexpected shortcomings with these methods. It provides some useful insights into understanding protein chemical shifts and suggests a new route to improving chemical shifts prediction. The RSS surfaces were incorporated into the program PRSI.