Alzheimer's disease is caused by accumulation of amyloid-beta (A beta) peptides in a brain. To suppress the production of Ap peptides, it is effective to inhibit the cleavage of amyloid precursor protein (APP) by secretases. However, because the secretases also play important roles to produce vital proteins for human body, inhibitors for the secretases may have side effects. To propose new agents for protecting the cleavage site of APP from the attacking of the -y-secretase, we have investigated here the specific interactions between a short APP peptide and curcumin derivatives, using protein-ligand docking as well as ab initio molecular simulations. (C) 2015 Elsevier B.V. All rights reserved.