A Theoretical reappraisal of polylysine in the investigation of secondary structure sensitivity of infrared spectra

Infrared spectroscopy has long provided a means to estimate the secondary structure of proteins and peptides. In particular, the vibrational spectra of the amide I' band have been widely used for this purpose as the frequency positions of the amide I' bands are related to the presence of specific secondary structures. Here, we calculate the amide I' IR spectra of polylysine in aqueous solution in its three secondary structure states, i.e., alpha-helix, beta-sheet, and random coil, by means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical computational methodology based on the perturbed matrix method (PM/vI). The computed spectra show a good agreement with the experimental ones. Although our calculations confirm the importance of the excitonic coupling in reproducing important spectral features (e.g., the width of the absorption band), the frequency shift due to secondary-structure changes is also well reproduced without the inclusion of the excitonic coupling, pointing to a role played by the local environment. Concerning the beta-conformation spectrum, which is characterized by a double-peak amide I' band due to excitonic coupling, our results indicate that it does not correspond to a generic antiparallel beta-sheet (e.g., of the typical size present in native proteins) but is rather representative of extended beta-structures, which are common in beta-aggregates. Moreover, we also show that the solvent has a crucial role in the shape determination of the beta-conformation amide I' band and in particular in the disappearance of the high-frequency secondary peak in the case of small sheets (e.g., 6-stranded)