# The effects of ferulic acid on $\beta$-amyloid fibrillar structures investigated through experimental and computational techniques

 Title The effects of ferulic acid on $\beta$-amyloid fibrillar structures investigated through experimental and computational techniques Publication Type Journal Article Year of Publication 2013 Authors Sgarbossa, A, Monti, S, Lenci, F, Bramanti, E, Bizzarri, R, Barone, V Journal Biochimica et Biophysica Acta - General Subjects Volume 1830 Pagination 2924–2937 ISSN 03044165 (ISSN) Keywords Amino Acid Sequence, Amyloid, amyloid beta protein, Amyloid beta-Peptides, Article, chemical analysis, Confocal, confocal microscopy, Coumaric Acids, ferulic acid, Fibrillogenesis inhibition, Fluorescence, Fourier Transform Infrared, gel permeation chromatography, hydrogen bond, Hydrogen Bonding, hydrophilicity, hydrophobicity, Hydroxycinnamic acid, Infrared spectroscopy, mathematical computing, Microscopy, molecular dynamics, molecular dynamics simulation, molecular mechanics, Molecular Sequence Data, nuclear magnetic resonance, priority journal, Protein aggregation, protein assembly, Protein Conformation, Protein Structure, Spectroscopy, X ray crystallography Abstract Background Current research has indicated that small natural compounds could interfere with $\beta$-amyloid fibril growth and have the ability to disassemble preformed folded structures. Ferulic acid (FA), which possesses both hydrophilic and hydrophobic moieties and binds to peptides/proteins, is a potential candidate against amyloidogenesis. The molecular mechanisms connected to this action have not been elucidated in detail yet. Methods Here the effects of FA on preformed fibrils are investigated by means of a concerted experimental-computational approach. Spectroscopic techniques, such as FTIR, fluorescence, size exclusion chromatography and confocal microscopy in combination with molecular dynamics simulations are used to identify those features which play a key role in the destabilization of the aggregates. Results Experimental findings highlight that FA has disruptive effects on the fibrils. The computational analysis suggests that dissociation of peptides from the amyloid superstructures could take place along the fibril axis and be primarily determined by the cooperative rupture of the backbone hydrogen bonds and of the Asp-Lys salt bridges. Conclusion FA clusters could induce a sort of stabilization and tightening of the fibril structure in the short term and its disruption in the long term, inhibiting further fibril re-assembly through FA screening effects. General significance The combination of experimental and computational techniques could be successfully used to identify the disrupting action of FA on preformed A$\beta$ fibrils in water solution. © 2012 Elsevier B.V. URL http://www.scopus.com/inward/record.url?eid=2-s2.0-84873723882&partnerID=40&md5=b05a4b8de003e4f09179ad54d83ce75c DOI 10.1016/j.bbagen.2012.12.023