Dissecting Two-Dimensional Ultraviolet Spectra of Amyloid Fibrils into Beta-Strand and Turn Contributions

Abstract

We present an analysis of the contributions of various secondary structure elements of the amyloid β-protein to the two-dimensional far ultraviolet (2DFUV) signal of an amyloid fibril model. The contributions of the turns and the β-strands are affected by the geometry of the backbone peptide amide π → π* transition dipoles, the backbone inter-amide coupling in the excited state, and the exciton delocalization. These contributions are clearly distinguishable in the xyxy-xyyx pulse polarization configuration. The differences are attributed to the smaller splitting of the exciton energies and the larger fluctuations of the geometry of the peptide amide π → π * transition dipoles at the turns, while make the 2DFUV signal sensitive to the secondary structure. This signal may be used to determine the proportion of turns and β -strands.

Spectroscopy in Complex Environments from QM–MM Simulations

“…A very interesting contribution to theoretical spectroscopy is due to Mukamel’s group, who developed methods for the simulation of two-dimensional electronic spectroscopy (2DES). − This technique has been in the limelight over the past decade or so, being an extension of 2D vibrational nonlinear spectroscopies into the visible region and, more recently, the UV region of the electromagnetic spectrum. − 2DES provides a wealth of information about electronic energy (and coherence) transfer between chromophoric groups and has been successfully applied to the study of multichromophoric systems, specifically photosynthetic light-harvesting antenna systems and core complexes. − However, because of the very high information density found in 2DES spectra, their interpretation is very challenging, and therefore, theoretical simulation methodologies have become a highly important tool. Accurate simulations of 2DES spectra require the inclusion of environmental effects such as polarization of the chromophores by the protein and solvent environments as well as the introduction of thermal band broadening.…”

Uncovering molecular relaxation processes with nonlinear spectroscopies in the deep UV

“…One of the next frontiers will be to carry out multi-dimensional spectroscopies at 200 nm [57]. It is well-known that optical properties of proteins are sensitive to secondary structure in this spectral range [42,43]. Studies of extraordinary organic photochemistries also motivate experiments at 200 nm [143].…”

“…Theoretical studies suggest that the nonlinear optical response of proteins is particularly sensitive to secondary structure near 200 nm, and multidimensional analogues of circular dichroism spectroscopies have even been proposed [42,43]. Also, with inspiration taken from studies of CHD and its derivatives, ultrafast photochemical reactions of cyclic monoalkenes in solutions can be explored because the pp ⁄ resonance of the C@C bond is near 200 nm.…”

“…Solutions to challenges including high-precision control over pulse delays and interferometric phase stability enabled subsequent applications in the visible wavelength range [40][41][42]. Further extension of 2D spectroscopy to the deep ultraviolet, hereafter termed 2DUV, is primarily motivated by biological systems whose lowest frequency resonances are found in this spectral range (200-300 nm) [43][44][45][46][47][48][49].…”

Ab initio simulations of two-dimensional electronic spectra: The SOS//QM/MM approach

“…The first 2DUV experiments have been finally reported and, therefore, 2DUV represents today the ultimate spectroscopy technique for studying systems whose lowest‐frequency electronic resonances are found in the UV (e.g., DNA, proteins, cycloalkanes, quinones, etc.). The ability of 2DUV spectroscopy to track structure and dynamics of biological systems containing UV‐active chormophores has been demonstrated by several theoretical studies carried out in the Mukamel's group . Using a Frenkel exciton matrix model, 2DUV spectra of amyloid fibrils can be simulated and used to characterize their structures.…”