Mapping the amide-I vibrations of model dipeptides with secondary structure sensitivity and amino acid residue specificity, and its application to amyloid β-peptide in aqueous solution.

Abstract

Vibrational spectroscopy has been known as particularly well-suited for deciphering the polypeptide's structure. To decode structural information encoded in IR spectra, we developed amide-I frequency maps on the basis of model dipeptides to correlate the amide-I frequency of interest to the combination of the calculated secondary structure dependent amide-I frequency by using DFT method and the electrostatic potentials that projected onto the amide unit from the micro-environment within molecular mechanics force field. The constructed maps were applied to model dipeptides and amyloid β-peptide fragment (Aβ25-35). The dipeptide specified map (DS map) and the hybrid map (HYB map) predicted amide-I bands of Aβ25-35 in solution satisfactorily reproduce experimental observation, and indicate the preference of forming β-sheet and random coil structure for Aβ25-35 in D2O just as the results of cluster analysis suggested. These maps with secondary structural sensitivity and amino acid residue specificity open up a way for the interpretation of amide-I vibrations and show their potentials in the understanding of molecular structure of polypeptides in solution.