Local Protein Backbone Folds Determined by Calculated NMR Chemical Shifts

NMR chemical shifts (CSs: delta N-NH, delta C-alpha, delta C-beta, delta C', delta H-NH, and delta H-alpha) were computed for the amino acid backbone conformers (alpha(L), beta(L), gamma(L), delta(L), epsilon(L), alpha(D), gamma(D), delta(D), and epsilon(D) [Perczel et al., J Am Chem Soc 1991, 113, 6256]) modeled by oligoalanine structures. Topological differences of the extended fold were investigated on single beta-strands, hairpins with type I and II beta-turns, as well as double-and triple-stranded beta-sheet models. The so-called "capping effect'' was analyzed: residues at the termini of a homoconformer sequence unit usually have different CSs than the central residues of an adequately long homoconformer model. In heteroconformer sequences capping effect ruins the direct applicability of several chemical shift types (delta H-NH, delta C', and delta N-NH) for backbone structure determination of the parent residue. Experimental delta H-alpha, delta C-alpha, and delta C-beta values retrieved from protein database are in good agreement with the relevant computed data in the case of the common backbone conformers (alpha(L), beta(L), gamma(L), and epsilon(L)), even though neighboring residue effects were not accounted for. Experimental and computed Delta delta H-alpha-Delta delta C-alpha, Delta delta H-alpha-Delta delta C-beta, and Delta delta C-alpha-Delta delta C-beta maps give qualitatively the same picture, that is, the positions of the backbone conformers relative to each other are very similar. This indicates that the H-alpha, C-alpha, and C-beta chemical shifts of alanine depend considerably on the backbone fold of the parent residue also in proteins. We provide tabulated CSs of the chiral amino acids that may predict the various structures of the residues. (C) 2011 Wiley Periodicals, Inc. J Comput Chem 32: 3362-3382, 2011