Predicting ¹⁵N chemical shifts in proteins using the preceding residue-specific individual shielding surfaces from φ, ψⁱ⁻¹, and χ¹torsion angles

Abstract

Empirical shielding surfaces are most commonly used to predict chemical shifts in proteins from known backbone torsion angles, φ and ψ. However, the prediction of ¹⁵N chemical shifts using this technique is significantly poorer, compared to that for the other nuclei such as ¹H^α, ¹³C^α, and ¹³C^β. In this study, we investigated the effects from the preceding residue and the side-chain geometry, χ¹, on ¹⁵N chemical shifts by statistical methods. For an amino acid sequence XY, the ¹⁵N chemical shift of Y is expressed as a function of the amino acid types of X and Y, as well as the backbone torsion angles, φ and ψⁱ⁻¹. Accordingly, 380 empirical `Preceding Residue Specific Individual (PRSI)' ¹⁵N chemical shift shielding surfaces, representing all the combinations of X and Y (except for Y=Pro), were built and used to predict ¹⁵N chemical shift from φ and ψⁱ⁻¹. We further investigated the χ¹ effects, which were found to account for differences in ¹⁵N chemical shifts by ∼5 ppm for amino acids Val, Ile, Thr, Phe, His, Tyr, and Trp. Taking the χ¹ effects into account, the χ¹-calibrated PRSI shielding surfaces (XPRSI) were built and used to predict ¹⁵N chemical shifts for these amino acids. We demonstrated that ¹⁵N chemical shift predictions are significantly improved by incorporating the preceding residue and χ¹ effects. The present PRSI and XPRSI shielding surfaces were extensively compared with three recently published programs, SHIFTX (Neal et al., 2003), SHIFTS (Xu and Case, 2001 and 2002), and PROSHIFT (Meiler, 2003) on a set of ten randomly selected proteins. A set of Java programs using XPRSI shielding surfaces to predict ¹⁵N chemical shifts in proteins were developed and are freely available for academic users at http://www.pronmr.com or by sending email to one of the authors Yunjun Wang (yunjunwang@yahoo.com).