Unveiling the Inhibitory Effect of Magnolol in the Aggregation of Human Calcitonin (hCT): A Comprehensive In-Silico Study.

Amyloid fibril formation by some peptides leads to several neurogenetic disorders. This limits their biological activity and increases cytotoxicity. Human calcitonin (hCT), 32 residue containing peptide, known for regulating calcium and phosphate concentration in the blood tends to form amyloids in aqueous medium. Polyphenols are very effective in inhibiting fibril formation. As part of our research, we have taken Magnolol (Mag), which is extracted from the Chinese herb Magnolia officinalis. To evaluate its effectiveness as an inhibitor in preventing hCT aggregation, we conducted an all-atom classical molecular dynamics simulation with varying concentrations of Mag. In presence of Mag, hCT maintains its helical conformation in higher order. Magnolol primarily interacts with hCT via van der Waals interaction. Asp15 residue of hCT, resides in the amyloid region (D₁₅FNKF₁₉) forms strong hydrogen bonding interaction with Mag. Moreover, aromatic residues of hCT interact with Mag through π-π stacking interactions. Our work gives insights into the molecular mechanism of Magnolol in the inhibition of hCT fibril formation to use it as a potential candidate for medicinal purpose.