The amide-I vibrational characteristics and conformational preferences of the model compound - histidine dipeptide (Ac-His-NHCH3, HISD) in gas phase and solution have been revealed with the help of ab initio calculations and wavefunction analyses. The Gibbs free energy surfaces (FESs) of solvated HISD were smoothed by solvent effect to exhibit different structural populations concerning various external environments. It was shown that the most stable conformations of HISD in CHCl3 and gas phase are C7eq, while those in DMSO and water are β and PPII, respectively. Compared with ALAD, the number of accessible conformational states on these FESs was predicted to be reduced due to the steric effect of imidazole group. The two amide-I normal modes of HISD were found to have intrinsically secondary structural dependencies, and be sensitive to surrounding environments. The average amide-Ia frequencies of HISD isomers in these environments were predicted to be almost the same as those of ALAD, while the amide-Ib mean frequencies were estimated to be lower than ALAD due to the intramolecular interactions between the imidazole group and amino-terminal amide unit. The good linear correlations between amide-I frequencies and the atomic electrostatic potentials (ESPs) of amide groups were also found to interpret the solvent-induced amide-I frequency shifts of HISD at the electronic structure level. These results allow us to gain a deep understanding of amide-I vibrations of HISD, and would be helpful for the site-specific conformational monitoring and spectral interpretation of solvated polypeptides.
Keywords: Amide-I mode; Electrostatic potential; Histidine dipeptide; Secondary structure; Solvent effect.
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