Ultraviolet Raman spectroscopy for understanding structure and formation mechanism of amyloid fibrils

Abstract Ultraviolet resonance Raman (UVRR) is a powerful tool for the study of biomolecular structure and dynamics including the secondary structure conformational analysis at the level of individual peptide bonds in large proteins. Deep ultraviolet resonance Raman (DUVRR) is uniquely suitable for structural characterization of proteins at all stages of amyloid fibril formation because it avoids interference from fluorescence, and selectively enhances the peptide backbone, making it suitable for the study of biological studies. The combination of hydrogen–deuterium exchange with DUVRR spectroscopy allows for probing the variations in cross-β core structure of fibril polymorphs. The application of advanced statistics, chemometrics, and two-dimensional correlation spectroscopy in particular for DUVRR spectra analysis significantly increases the quality and amount of information on protein structure and dynamics. This approach is especially useful for establishing the kinetic mechanisms of amyloid fibrillation, which is associated with numerous human diseases.