Aggregation of amyloid beta (Aβ) peptides leads to formation of fibrilar, soluble oligomers, and their deposition is a key event in progression of Alzheimer’s disease (AD). Recent experimental studies of… Click to show full abstract
Aggregation of amyloid beta (Aβ) peptides leads to formation of fibrilar, soluble oligomers, and their deposition is a key event in progression of Alzheimer’s disease (AD). Recent experimental studies of Arg-Arg-7-amino-4-trifluoromethylcoumarin (RR-AFC) showed significant Aβ aggregation inhibition, but its molecular mechanism is not yet clear. Hence, the present study aims at exploring the underlying mechanism of destabilization and inhibition of aggregation of the Aβ protofibril by RR-AFC at the molecular level. Molecular docking analysis shows that RR-AFC binds to chain A of the Aβ protofibril through hydrogen bonding interactions. Comparative molecular dynamics simulations depict the binding of RR-AFC at the edge of chain A, and its partially inserted conformation at the hydrophobic core destabilizes the Aβ protofibril. Its binding causes loss of hydrophobic contacts, leading to a partial opening of tightly packed β-sheet protofibrils. The hydration effect of salt bridge between the amino group of Lys...
               
Click one of the above tabs to view related content.