Inhibition of the Amyloid-Beta Protein Aggregation with Polyphenol Drugs using Computational Chemistry

Gage J. Dudkowski
Dr. Andrew Kauffmann and Dr. Bill R. Miller (A.T. Still University), Faculty Mentors

Alzheimer’s Disease is a neurodegenerative disorder affecting nearly 7 million Americans, which increases yearly. A commonality among Alzheimer’s patients is the presence of amyloid-β plaques in the brain which contain high concentrations of amyloid-β peptides. These peptides aggregate in β-sheet structures allowing them to stabilize and progress Alzheimer’s. Polyphenols appear to be potential inhibitors of this aggregation in its formation stages due to its hydrophobic and antioxidant properties. Study uses multiple computational chemistry methods including molecular docking and molecular dynamics to find the best binding site for a ligand, and then simulate the protein-ligand interactions. The simulations are analyzed to study disaggregation of the  amyloid-β protein. We investigated sixteen different polyphenols and simulated each at four different concentrations to 5000 ns. Our simulations reveal significant differences in binding affinity and disruption of the amyloid-β plaque that is prevalent in Alzheimer’s Disease.

Keywords: Alzheimer's, Amyloid-Beta, Computational, Chemistry, Polyphenols, Protein, Neurodegenerative, Brain

Topic(s):Chemistry
Biochemistry and Molecular Biology
Biology

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA