Investigation of Some Inhibitors of Alzheimer Associated Amyloid Beta Aggregation by Quantum Optimization and Molecular Docking Simulation

Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to the death of brain cells and cognitive decline. Aggregation of extracellular amyloid plaque containing amyloid β- peptide (Aβ) and intracellular neurofibrillary tangles containing tau protein is two main causes of Alzheimer s disease [1]. The most abundant forms of Aβ are the Aβ1–40 and Aβ1–42. Aβ42 is more prone to self-assemble and therefore more toxic than Aβ40B [2]. This study is a report of quantum mechanics-guided ligand optimization and docking of six plant-based compounds against two forms of Aβ42 (PDB ID: 2BEG and 2MXU). The three-dimensional (3D) structures of the ligands were built and their geometries were optimized through Gaussian 09W. The molecular docking and 2D ligand interactions were conducted by Molsoft ICM-Pro 3.8-6a. The results indicated that binding to the 2BEG fibril was more desirable than to 2MXU. Docking results show that the semi-empirical binding energy (ICM score) between Curcumin, Rosmarinic Acid, Apigenin, Quercetin, Melatonin, O-vanillin with 2BEG are about to -26.07, -22.39, -21.05, -20.82, -16.57, -15.35 kcal/mol, respectively. Among them, curcumin represents more stable interaction energy (-26.07). The most important interaction is hydrogen bond that is formed between O of CO with G37 in a distance around 2.634 Å and another between H of OH with L17 which had 3.178 Å length.