Calculation of the spectral properties The spectra were calculated using the two-step procedure (polar=ROA) with a 6-31++G(d) basis set, as diffuse functions are much more important for the calculation of the spectral properties than they are for the optimization and frequency calculation. Realistic line shapes were simulated using one Lorentzian function for each normal mode with a full-width at half maximum of 10 cm -1 for the IR spectra and 20 cm -1 for the Raman and ROA spectra, respectively. Wavenumber scaling of the computed IR, Raman and ROA spectra Since the wavenumbers in the DFT calculated spectra are overestimated due to inter alia the harmonic approximation, a global scaling factor is typically multiplied to the entire wavenumber dimension to allow a direct comparison of the experimental and the simulated spectra. Since the amide I (and I') band (mainly amide C=O stretching) is known to be even more overestimated due to, for example, basis set dependence, and interaction with the solvent (see also below) a separate scaling factor needs to be applied to the amide I vibrations compared to the remainder of the spectrum. As shown in Figure for the FT-IR spectra, a scaling factor of 0.95 for the amide I' and a global scaling factor of 1.0 (so no scaling) needs to be multiplied with the wavenumber dimension (x-axis). The top panel shows the weighted average of the 20 most populated clusters. The spectrum of each of the 20 clusters is shown in Figure . Since the Raman and ROA spectra have more complex spectral features than the FT-IR spectrum, the comparison of the simulated spectra with experiment is more challenging. Furthermore, the calculated spectra show some bands that are not found in experiment. Since this complicates the determination of a proper scaling factor, the scaling factor of 0.95 is again applied to the amide I vibrations and a global scaling factor of 0.987 that is commonly reported in Raman/ROA calculations at this level of theory is applied to the remainder of the spectrum (<1675 cm -1 ). In Figure , it is shown that using these scaling factors, the amide I around S11 1680 cm -1 aligns better with experiment, while for the remainder of the spectrum, we must be careful in assigning specific bands in the experiment based on the calculated bands. Each individual spectrum after scaling is plotted in Figure . Although the implicit solvent model (C-PCM) accounts for solvent-solute interactions of the peptide with water, hydrogen bonding with the solvent is not explicitly taken into account.