Simulation of IR, Raman and VCD amide I band profiles of self-assembled peptides

Abstract

Vibrational spectroscopy is a suitable and convenient tool to probe the self-assembly of peptides, a biomedically and biotechnologically relevant process. Theoretical efforts to quantitatively analyze vibrational spectra of peptide aggregates have thus far focused on exploring the IR and to a lesser extent the vibrational circular dichroism (VCD) spectra of rather small sized planar or nearly planar β-sheet structure. The current study utilizes an algorithm based on an excitonic coupling model with experimentally or computationally determined parameters to simulate the amide I band profiles of the IR, isotropic Raman, anisotropic Raman and VCD spectra of two-and three-dimensional β-sheet structures. In agreement with earlier calculations we found that the splitting between the two prominent IR bands of an antiparallel β-sheet increases with increasing number of strands until a saturation is reached at approximately eight strands. The dominant isotropic and anisotropic Raman bands of amide I are located between the two IR bands and downshift only slightly with increasing sheet length. The VCD signal is rather weak. We also investigated the influence of sheet stacking on amide I by calculating the respective IR, Raman and VCD profiles for two in-register, facially stacked β-sheets with seven strands per sheet for an antiparallel arrangement of the sheets and six strands per sheet for a parallel arrangement. We found that stacking produces additional bands in the IR and Raman spectrum, in line with the reduced symmetry of the ideal unit cell of the β-sheet. In addition, a more pronounced VCD signal is detected. A comparison with experimental IR, Raman and VCD spectra of gelated (AAKA) 4 reveals a good qualitative agreement between experimental and simulated amide I band profiles.

Vibrational Circular Dichroism as a Probe of Fibrillogenesis: The Origin of the Anomalous Intensity Enhancement of Amyloid-like Fibrils

“…A change of the still rather regular geometry of the model would lead to a broader distribution of intensities, particularly in the region between the two bands obtained for the aa configuration. 29 This could explain the asymmetric couplets observed for fibrils of larger systems, such as insulin and lysozyme, obtained by Ma et al 20 ' CONCLUSION We have demonstrated the use of VCD to probe the fibril formation kinetics of a short amyloidogenic peptide. Fibril formation results in an enhanced signal in the amide I region of the corresponding VCD spectrum.…”

Light-Triggered Disassembly of Amyloid Fibrils

“…28 This larger splitting may indicate that the photocage facilitates a tighter packing of neighboring strands. 30,31 Atomic force microscopy (AFM) images of the incubated sample show the presence of typical amyloid fibrils (Figure 2). The mature aggregates are similar in morphology to those formed by the wild-type peptide 18 and, as observed for full-length Aβ 1-40 32 contain a mixture of both rod-like and twisted fibrils.…”

Amide I band and photoinduced disassembly of a peptide hydrogel

“…As indicated (Figure 3B), while the amide I′ band of the KFE8-C peptide also shows that it forms antiparallel β-sheets, the high-frequency amide I′ component (i.e., the peak at ~1685 cm −1 ) shows an unusually large enhancement, in comparison to that of the wild-type KFE8 peptide and other peptide fibrils consisting of antiparallel β-sheets. As this band corresponds to the totally symmetric representation of the antiparallel β-sheet unit cell, it is typically only weakly IR active [40,42–46]. While the strongly enhanced absorptivity of the 1685 cm −1 component is certainly very interesting, we cannot offer a definitive mechanistic interpretation of this intensity enhancement.…”