Fast and accurate computation of the 13C chemical shifts for an alanine-rich peptide.
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 13Calpha and 13Cbeta chemical shifts to distinguish the PP(II) conformation from the alpha-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 PP(II) helical region of the Ramachandran map.
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
Jorge A
JA
Vila
Héctor A
HA
Baldoni
Daniel R
DR
Ripoll
Harold A
HA
Scheraga
D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002247:Carbon Isotopes; D002942:Circular Dichroism; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D009010:Monte Carlo Method; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D013816:Thermodynamics
D000596:Amino Acids; D002247:Carbon Isotopes; D009842:Oligopeptides; D000409:Alanine