Fast and accurate computation of the 13 C chemical shifts for an alanine‐rich peptide

Abstract

The purpose of this work is, first, to present a fast and accurate technique to compute Boltzmann-averaged values of the quantum-chemical 13C chemical shifts for each amino acid in oligopeptides, demonstrated here by an application to the peptide Ac-XXAAAAAAAOO-NH2 (where X denotes diaminobutyric acid, A is alanine, and O is ornithine) [XAO] and, second, to discuss the capability of the 13Cα and 13Cβ chemical shifts to distinguish the PPII conformation from the α-helix and statistical-coil conformations. Use is made of a combination of approaches, summarized as follows: (1) derivation of an ensemble of conformations by using a molecular mechanics technique; (2) use of a clustering procedure to form families and build a reduced set of conformations consisting of the lowest-energy conformations of each family, and (3) computation of the 13C chemical shifts for the lowest-energy conformations of each family, using a quantum-chemical approach that treats a selected residue, or group of residues, with a 6-311+G(2d,p) locally-dense basis set, while the remaining residues in the sequence are treated with a 3-21G basis set. The whole procedure is quite accurate and speeds up the computation of the Boltzmann-averaged values of the 13C-chemical shifts by several orders of magnitude. The present application sheds some light on the conformational preference for alanine and non-alanine residues to occupy the PPII helical region of the Ramachandran map. Proteins 2004. © 2004 Wiley-Liss, Inc.The purpose of this work is, first, to present a fast and accurate technique to compute Boltzmann-averaged values of the quantum-chemical 13C chemical shifts for each amino acid in oligopeptides, demonstrated here by an application to the peptide Ac-XXAAAAAAAOO-NH2 (where X denotes diaminobutyric acid, A is alanine, and O is ornithine) [XAO] and, second, to discuss the capability of the 13Cα and 13Cβ chemical shifts to distinguish the PPII conformation from the α-helix and statistical-coil conformations. Use is made of a combination of approaches, summarized as follows: (1) derivation of an ensemble of conformations by using a molecular mechanics technique; (2) use of a clustering procedure to form families and build a reduced set of conformations consisting of the lowest-energy conformations of each family, and (3) computation of the 13C chemical shifts for the lowest-energy conformations of each family, using a quantum-chemical approach that treats a selected residue, or group of residues, with a 6-311+G(2d,p) locally-dense basis set, while the remaining residues in the sequence are treated with a 3-21G basis set. The whole procedure is quite accurate and speeds up the computation of the Boltzmann-averaged values of the 13C-chemical shifts by several orders of magnitude. The present application sheds some light on the conformational preference for alanine and non-alanine residues to occupy the PPII helical region of the Ramachandran map. Proteins 2004.