Abstract
Nuclear magnetic shielding interaction of backbone nuclei is the most direct probe of secondary structure of proteins due to its wide variation in shielding parameters in response to changes in electronic environments. In this report, we demonstrate the exclusive sensitivity of backbone amide 15N chemical shielding tensor (CST) components to the two adjacent dihedral angles \({\psi}_{i-1}\) and \({\phi}_{i}\) of the amide group using density functional studies of the central alanine residue of a model tripeptide N-formyl–glycyl–alanyl–leucine–amide. Especially, we show that \({\psi}_{i-1}\) has a dominant effect on the 15N principal components \({\sigma}_{11}\) and \({\sigma}_{22}\) , whereas \({\phi}_{i}\) affects \({\sigma}_{22}\) and \({\sigma}_{33}\) the most. Through the construction of theoretical 15N shielding surfaces of the model tripeptide as functions of \({\psi}_{i-1}\) and \({\phi}_{i}\) , the predicted 15N CSTs are compared with direct 15N shielding calculations for 20 alanine-containing tripeptide segments selected randomly from regular α-helical and β-sheet regions of 13 protein structures available in the literature. In contrast to the poor correlation observed for α-helical segments, β-sheet segments exhibit a significant correlation between shielding-surface-predicted and directly calculated 15N shielding components with \({\sigma}_{22}\) and \({\sigma}_{\text{i}\text{s}\text{o}}\) having the largest correlation, in agreement with experimental 15N chemical shift studies in the literature. Using alanine as a model for other amino acid types, a similar comparison between the alanine-based 15N shielding and the direct 15N CST calculations for 38 tripeptide segments with non-alanine central residues from sheet regions of four proteins reaffirms the unique sensitivity of \({\sigma}_{22}\) and \({\sigma}_{\text{i}\text{s}\text{o}}\) to backbone dihedral angles irrespective of the identity of side chains.
Graphical abstract
