As far as the predicted ROA response is concerned, the weighted-average spectrum shows very limited convergence with increasing the number of averaged conformers (Fig )). This is not surprising, given that a single calculated ROA spectrum is strongly influenced by contributions of the side chains conformations, while most contributions of the dynamic and achiral side chains cancel out. To achieve a better agreement with experiment, a larger number of conformers and side chain rotamers would be necessary. However, the positive band in the amide I region (at about 1680 cm -1 ) is observed in all calculated ROA spectra and in good agreement with the experiment, pointing towards an overall disordered structure of the peptide. This positive band in the amide I region of the ROA spectrum, as well the positive band around 1318 cm -1 in the amide III region, are typically assigned to short stretches of PPII backbone conformation of intrinsically disordered peptides and proteins. As a proof-of-concept, we used a regular PPII conformation (all Φ angles -75 • and all Ψ angles 145 • ) of this peptide and created 20 different arrangements of the side chains (different rotamers) to better sample the side chain flexibility (Fig. ). Comparing calculated IR and Raman spectra for the canonical PPII structures with rotational averaging of the side chains did not result in a considerable improvement. However, the resulting average ROA spectrum of this test set resembles the spectral features we observed in our experimental ROA spectrum (Fig. ), such as the positive amide I band at 1680 cm -1 and the -/+ couplet at 1260/1318 cm -1 , which are dominated by spectral features associated with PPII structures. Notably, some of these PPII backbone based rotamers show a negative signal in the amide III region, which is often not shown in PPII reference spectra, e.g.