Vibrational Spectral Signatures of Peptide Secondary Structures: N-methylation and Side chain Hydrogen Bond in Cyclosporin A

Molecular dynamics simulations are performed to explore important conformations of cyclosporin A, an immunosuppressive cyclic undecapeptide drug, in different media including gas-phase, chloroform, and acetonitrile. Density functional theory calculations are used to refine the low-lying conformers and to predict their infrared and vibrational circular dichroism spectra. Vibrational spectral signatures in the important amide II, I, and A regions are identified for typical peptide secondary structures including beta-turn (type II' or I), antiparallel beta-sheet (flat or twisted), inverse gamma-turn, N-methylated peptide bond, and side chain H-bond. New insights into the spectral signatures of secondary structures especially with N-methylation and side chain hydrogen bond are provided, which can be very useful for further peptide conformation analysis in general. (C) 2011 Wiley Periodicals, Inc. J Comput Chem 32: 1500-1518, 2011