2. Academic Validation
  3. Estimating AChE inhibitors from MCE database by machine learning and atomistic calculations

Estimating AChE inhibitors from MCE database by machine learning and atomistic calculations

  • J Mol Graph Model. 2025 Jan:134:108906. doi: 10.1016/j.jmgm.2024.108906.
Quynh Mai Thai 1,  Trung Hai Nguyen 2,  George Binh Lenon 3,  Huong Thi Thu Phung 4,  Jim-Tong Horng 5,  Phuong-Thao Tran 6,  Son Tung Ngo 7
Affiliations

Affiliations

  • 1 Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam. Electronic address: thaiquynhmai@tdtu.edu.vn.
  • 2 Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
  • 3 School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
  • 4 NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam.
  • 5 Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
  • 6 Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, 008404, Viet Nam.
  • 7 Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Viet Nam. Electronic address: ngosontung@tdtu.edu.vn.
PMID: 39561662 DOI: 10.1016/j.jmgm.2024.108906
Abstract

Acetylcholinesterase (AChE) is one of the most successful targets for the treatment of Alzheimer's disease (AD). Inhibition of AChE can result in preventing AD. In this context, the machine-learning (ML) model, molecular docking, and molecular dynamics calculations were employed to characterize the potential inhibitors for AChE from MedChemExpress (MCE) database. The trained ML model was initially employed for estimating the inhibitory of MCE compounds. Atomistic simulations including molecular docking and molecular dynamics simulations were then used to confirm ML outcomes. In particular, the physical insights into the ligand binding to AChE were clarified over the calculations. Two compounds, PubChem ID of 130467298 and 132020434, were indicated that they can inhibit AChE.

Keywords

AChE; Free Energy Perturbation; Mechine learning; Molecular docking; Molecular dynamics.

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