Programme

P.49 -- Poster, VCTP-48

Date: Thursday, 3 August 2023

Time: 08:30 - 10:00

Searching for AChE inhibitors from natural compounds by using machine learning and atomistic simulations

Quynh Mai Thai (a) , T. Ngoc Han Pham (a) , Dinh Minh Hiep (b), Minh Quan Pham (c,d) , Phuong-Thao Tran (e) , Trung Hai Nguyen (f,g) , Son Tung Ngo (a,h)

(a) Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam (b) Department of Agriculture and Rural Development, Ho Chi Minh City, Viet Nam (c) Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Viet Nam (d) Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Viet Nam (e) Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Viet Nam (f) Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City, Viet Nam (g) Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam (h) Laboratory of Theoretical and Computational Biophysics, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Viet Nam

Acetylcholinesterase (AChE) is one of the most important drug targets for Alzheimer's disease treatment. It hydrolyzes neurotransmitter acetylcholine resulting a deficiency of acetylcholine in brain and also common cause of Alzheimer’s disease. Therefore, In this work, we used combined approach involving machine learning (ML) model and atomistic simulations (molecular docking, steeredmolecular dynamics simulations) was established to predict the ligand binding affinity of Vietnamese compounds to AChE. First, GraphConv model was selected and utilized to rapidly and accurately screen the natural compound database for potential AchE inhibitors. Then, atomic simulations were used to confirm that result, and 20 compounds be able to inhibit AChE were proposed through this good agreement. Especially, four compounds including geranylgeranyl diphosphate, 2-phosphoglyceric acid, and 2-carboxy-d-arabinitol 1-phosphate, and farnesyl diphosphate were predicted to be potential AChE inhibitors. These compounds with log(BB) in the range of −0.59 to 0.00 were able to cross the blood-brain barrier. Moreover, the hERG inhibition index showed that these compounds could not have toxicity to the human body. Overall, our obtained results may stimulate the search potentials drugs for an Alzheimer’s disease therapy.

Presenter: Thai Quynh Mai