Abstract
NMR–chemical shift structure correlations were investigated by using GIAO‐RB3LYP/6‐311++G(2d,2p) formalism. Geometries and chemical shifts (CSI values) of 103 different conformers of N′‐formyl‐L‐histidinamide were determined including both neutral and charged protonation forms. Correlations between amino acid torsional angle values and chemical shifts were investigated for the first time for an aromatic and polar amino acid residue whose side chain may carry different charges. Linear correlation coefficients of a significant level were determined between chemical shifts and dihedral angles for CSI[^1^H^α^]/φ, CSI[^13^C^α^]/φ, and CSI[^13^C^α^]/ψ. Protonation of the imidazole ring induces the upfield shift of CSI[^13^C^α^] for positively charged histidines and an opposite effect for the negative residue. We investigated the correspondence of theoretical and experimental ^13^C^α^, ^13^C^β^, and ^1^H^α^ chemical shifts and the nine basic conformational building units characteristic for proteins. These three chemical shift values allow the identification of conformational building units at 80% accuracy. These results enable the prediction of additional regular secondary structural elements (e.g., polyProlineII, inverse γ‐turns) and loops beyond the assignment of chemical shifts to α‐helices and β‐pleated sheets. Moreover, the location of the His residue can be further specified in a β‐sheet. It is possible to determine whether the appropriate residue is located at the middle or in a first/last β‐strand within a β‐sheet based on calculated CSI values. Thus, the attractive idea of establishing local residue specific backbone folding parameters in peptides and proteins by employing chemical shift information (e.g., ^1^H^α^ and ^13^C^α^) obtained from selected heteronuclear correlation NMR experiments (e.g., 2D‐HSQC) is reinforced. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1307–1317, 2005