Solvent effects on IR and VCD spectra of helical peptides: DFT-based static spectral simulations with explicit water

Simulations of IR and VCD spectra are carried out for model alpha-helical, 3(10)-helical, and 3(1)-helical (polyProII-like) oligopeptides, with up to 21 amide groups, and including explicit consideration of effects of directly hydrogen-bonded solvent (water). Parameters used were obtained from ab initio density functional theory (DFT) computations of force field, atomic polar and axial tensors for oligopeptides of 5 to 7 amides, whose structures were constrained in (phi,psi) to target the secondary structure type but otherwise fully optimized. By comparison with experimental data as well as with calculations for identical but isolated (gas phase) peptides, the computed effects of an inner shell of aqueous solvent on the vibrational spectra of helical oligopeptides are illustrated. The interaction with solvent causes significant frequency shifts of the amide bands, but only minor changes in the characteristic IR intensity distributions and splittings and the VCD band shapes. Better agreement with experimental band shapes is achieved for the alpha-helical amide I' (N-deuterated) VCD by inclusion of explicit solvent in the calculations. Some improvements are also observed in theoretical VCD predictions for 13C labeled alpha-helical peptides when solvated models are used. However, the qualitative isotopic splitting patterns are preserved and just shifted in frequency due to consistent, solvent independent interamide coupling constants. The critical match of experiment and theory for relative positions of transitions in peptides with specifically separated 13C=O labels, including and neglecting solvent, confirms the stability of the coupling interactions. Despite these solvation effects, the calculated VCD band shape of the amide I mode is shown to be a reliable conformational probe, since it remains basically insensitive to frequency shifts caused by environment. Thus theoretical VCD simulations, even vacuum calculations, are shown to provide useful spectral predictions for solution-phase peptides.