Determination of Dihedral Angles in Peptides through Experimental and Theoretical Studies of α-Carbon Chemical Shielding Tensors

A simple method for the determination of backbone dihedral angles in peptides and proteins is presented. The chemical-shift anisotropies (CSA) of the central alanine α-carbon in powdered crystalline tripeptides, whose structures have been determined previously by X-ray crystallography, were measured by cross-polarization magic-angle-spinning nuclear magnetic resonance. The experimental CSA values were correlated with ab initio chemical-shielding calculations over Ramanchandran φ/ψ space on an N-formyl-l-alanine amide fragment. Using this correlation, φ/ψ probability surfaces for one of the tripeptides were calculated based only on the α-carbon CSA, allowing a prediction of backbone angles. Dihedral angles predicted by these calculations fall within ±12° of the values determined by crystallography. This approach should be useful in the determination of solid-state protein structure.