Polyglutamic acid (PGA) is an excellent model system to study peptide and protein folding. Its conformation in solution can be conveniently studied by vibrational optical activity. To better understand the behavior of the molecule in different protonation states and advance the spectroscopic methodology, we obtained infrared (IR), vibrational circular dichroism (VCD), Raman, and Raman optical activity (ROA) spectra of various PGA forms and interpreted them on the basis of molecular dynamics (MD) and density functional theory (DFT) computations. The spectra include the ROA of PGA fibrils, which have been rather unexplored so far. The fibrils provided a distinct ROA pattern, which could be verified by the measurement of both enantiomers. Advancements in the use of vibrational spectroscopy for amyloid fibrils may contribute to the understanding of the biological role of these protein forms, often accompanying neurodegenerative diseases. The computations provided a reliable link between the spectral shapes and molecular geometry, and the simulated spectra reproduced the most important experimental features, although band-to-band simulations of the fibril vibrational optical activity remain challenging. The results nevertheless clearly show that vibrational optical activity combined with spectral simulations appears as a handy tool to study the geometry of proteins, including their aggregates.

Department of Optics Palacký University Olomouc 17 Listopadu 12 77900 Olomouc Czech Republic

Institute of Organic Chemistry and Biochemistry Academy of Sciences Flemingovo Náměstí 2 16610 Prague Czech Republic

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