Still, the agreement between the theoretically predicted observables and the experiments crucially depends on the accuracy of the employed methods. First, optimized force-fields are required to sample correctly the conformational phase space of disordered peptides (such as the here-employed Charmm36m 57 ) whereas more traditional protein force fields have the tendency of over-structuring the ensemble. Second, analysis of the conformational phase space requires the application of structural metrics in a high-dimensional space and of dimensionality-reduction algorithms, such as the sketch-map method employed here, for adequate visual representations (Fig. ). Third, the spectral response of each conformer must be computed at a high level of accuracy. In particular, we could not reproduce the experimental CD spectrum using basis-set-based approaches optimized for well-structured protein systems, as was possible for ordered peptides. A novel QM/MMPol approach based on TD-DFT calculations on the backbone amide chromophores embedded in the electrostatic field of the rest of the peptide and the solvent has led, instead, to very good agreement with the experiment (Figs. and). In doing so, it became clear that the main features of the experimental spectrum could be reproduced only after including ordered conformers.