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, although 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 phenol soluble modulin α3. 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 broadband 2DIR simulations lead to characteristic signals that are sensitive to fibril length and match the experimental 2DIR spectra.