Ab initio molecular simulations on specific interactions between amyloid-β peptide and new curcumin derivatives

Accumulation of amyloid-β (Aβ) peptides in a brain is closely related with the pathogenesis of Alzheimer's disease. To suppress the production of Aβ peptides, many kinds of agents have been developed for inhibiting the cleavage of amyloid precursor protein (APP) by secretases. However, because the secretases also play important roles the production of vital proteins for the human body, inhibitors for the secretases may have side effects. In the present study, to propose new agents for protecting the cleavage site of APP from the attacking of the γ-secretase, we investigate the specific interactions between a short APP peptide and curcumin derivatives, using protein-ligand docking as well as ab initio molecular simulations. Our proposed derivatives (curcumin VI and IX) are found to have a large binding energy with APP, and they are expected to be a potent inhibitor to the production of Aβ peptides.