SYNERGY BETWEEN EXPERIMENTAL AND MOLECULAR DOCKING FOR IDENTIFYING NATURAL THERAPEUTIC COMPOUNDS AGAINST ALZHEIMER'S DISEASE

Abstract

Excessive hydrolysis of acetylcholine, a signaling molecule between neurons, by acetylcholinesterase (AChE) is crucial in the development of Alzheimer's disease. Modulation of AChE activity in the presence of the indigenous plant species from Montenegro extract leads to the inhibition of acetylcholine binding to AChE. The investigated plant extract contains several potential AChE inhibitors. To avoid lengthy and expensive experimental testing for each constituent of the extract, molecular docking calculations were performed. The total binding energies were monitored, and the interactions of individual compounds with AChE were analyzed. Compared to the acetylcholine, all active substances from the extract formed more stable adducts with both closed and open forms of AChE. Therefore, all investigated substances have the potential for competitive inhibition of acetylcholine binding to the active site in AChE. Considering their concentrations in the extract, catechin and gallic acid were selected for separate experimental docking, confirming the results of molecular docking calculations. Combining experimental and molecular docking techniques, experimental research volume and time were significantly reduced, as well as the quantity of chemicals used. Besides, the costs and time required to discover potential natural remedies for treating Alzheimer's disease were also decreased.