A Theoretical Analysis of Coherent Cross-Peaks in Polarization Selective 2DIR for Detection of Cross-α Fibrils

The coupled amide-I vibrational modes in peptide systems such as fibrillar aggregates can often provide a wealth of structural information, though the associated spectra can be difficult to interpret. Using exciton scattering calculations, we characterized the polarization selective 2DIR peak patterns for cross-α peptide fibrils, a challenging system given the similarity between the monomeric and fibrillar structures, and interpret the results in light of recently collected 2D data on the cross-α peptide PSMα3. We find that stacking of α-helices into fibrils couples the bright modes across helical subunits, generating three new Bloch-like extended excitonic states that we designate A⏊, E∥, and E⏊. Coherent superpositions of these states in broad-band 2DIR simulations lead to characteristic signals that are sensitive to fibril length, and match the experimental 2DIR spectra.