Secondary structural effects on protein NMR chemical shifts

Abstract

For an amino acid in protein, its chemical shift, δ(ϕ, ψ)_s, is expressed as a function of its backbone torsion angles (ϕ and ψ) and secondary state (s): δ(ϕ, ψ)_{s=δϕ, ψ)_coil+Δδ(ϕ, ψ)_s}, where δ(ϕ, ψ)_coil represents its chemical shift at coil state (s=coil); Δ δ(ϕ, ψ)_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 ¹³CO, ¹³Cα, ¹³Cβ,¹Hα, ¹⁵N, and ¹HN 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 Δ δ(ϕ, ψ)_sheet and Δ δ(ϕ, ψ)_helix were found varying little with backbone conformation and the 20 amino acids, specifically for ¹³CO, ¹³Cα, and ¹Hα 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 [Wang and Jardetzky, J. Biomol. NMR, 28: 327–340 (2004)], which is available for academic users at http://www.pronmr.com or by sending email to the author (yunjunwang@yahoo.com).