Alzheimer’s Disease (AD) is a neurodegenerative disorder that is the 5th leading cause of death in individuals aged 65 or older. One hypothesis to the origin of AD is the amyloid hypothesis, theorizing that neural degradation is caused by the aggregation of Amyloid-β (Aβ) plaques in the neural synapse. Stilbenoid molecules, such as Diethylstilbestrol and Calebin-A, have shown to be promising inhibitors to the aggregation of Aβ in vitro, breaking down the β-sheet secondary structure that stabilizes the Aβ aggregates.<br/>Computational modeling is used to determine the binding interactions between the polyphenol drug and Aβ (Molecular Docking) and then simulate the further unrestrained interactions between Aβ and the polyphenols (Molecular Dynamics). The 2000 nanosecond (ns) simulations are then analyzed to determine the stability of the structure of Aβ through their length and map the drug interactions that may contribute to the instability and breakdown of Aβ such as hydrogen bonding as well as van der Waals, pi stacking, and nonpolar interactions that compose the drug’s binding free energy to the peptide. From understanding the protein-drug interactions that destabilize Aβ, improved therapeutics can be developed for the treatment of AD.

Computational investigation of the role of polyphenols in the disaggregation of amyloid-β oligomers associated with Alzheimer’s disease

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.