Two-dimensional near-ultraviolet spectroscopy of aromatic residues in amyloid fibrils: a first principles study

We report a first principles study of two dimensional electronic spectroscopy of aromatic side chain transitions in the 32-residue β-amyloid (Aβ(9-40)) fibrils in the near ultraviolet (250-300 nm). An efficient exciton Hamiltonian with electrostatic fluctuations (EHEF) algorithm is used to compute the electronic excitations in the presence of environmental fluctuations. The through-space inter- and intra-molecular interactions are calculated with high level quantum mechanics (QM) approaches, and interfaced with molecular mechanics (MM) simulations. Distinct two dimensional near ultraviolet (2DNUV) spectroscopic signatures are identified for different aromatic transitions, and the couplings between them. 2DNUV signals associated with the transition couplings are shown to be very sensitive to the change of residue-residue interactions induced by residue mutations. Our simulations suggest that 2DNUV spectra could provide a useful local probe for the structure and kinetics of fibrils.