Polyphenol Interactions with Amyloid Fibrils: A Molecular Docking Study
Abstract
Polyphenols, a versatile group of naturally occurring compounds with many favorable biological properties currently attract increasing research interest in the context of their ability to inhibit the formation and to destabilize special protein aggregates, amyloid fibrils, associated with a number of human diseases. In the present study the molecular docking technique was used to gain insights into molecular details of the interactions between polyphenolic compounds such as quercetin, curcumin, resveratrol, sesamin, salicylic and gallic acids with the mature amyloid fibrils from Abeta peptide, islet amyloid polypeptide, insulin, apolipoprotein A-I and apolipoprotein A-II. All examined polyphenols displayed the highest binding affinities for amyloid fibrils from apolipoprotein A-II and insulin, while the lowest affinities were observed for the fibrillar apolipoprotein A-I. The hydrophobicity/hydrophilicity analysis of amino acid composition of the binding sites showed that hydrophobic and neutral residues play a predominant role in the polyphenol complexation with amyloid fibrils from apolipoprotein A-I, apolipoprotein A-II and insulin, the basic residues essentially contribute to polyphenol association with fibrillar Abeta and islet amyloid polypeptides, while the involvement of acidic residues was revealed only for the complexes sesamin + apolipoprotein A-I / Abeta fibrils and curcumin keto + insulin fibrils. The results obtained may prove useful in the development of novel polyphenol-based anti-amyloid strategies.
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