Natural-based AChE inhibitors widely are used to treat Alzheimer's disease treatments nowadays. ZINC000253412911 is a natural compound having the potency to have AChE inhibitory activity. This study aimed to determine the interaction and stability of the ZINC000253412911-AChE complex through molecular docking and 15-ns molecular dynamics (MD) simulations using YASARA-Structure. This study revealed that 100 best-redocked poses had RMSD values ≤ 2.000 Å, which indicated that the protocol was valid and could be used for molecular docking. Molecular docking results produced 3 clusters of the ZINC000253412911-AChE conformational poses. The interactions formed were hydrogen, aromatic, and hydrophobic. The results of MD simulations showed that two of the three poses were stable with the ΔRMSD values ≤ 2,000 Å. The average binding energy of the three poses of the complex were 8.286 ± 1.100, 9.680 ± 0.508, and 9.878 ± 0.584 kJ/mol. Hydroxyl groups and aromatic rings played a dominant role in stabilizing the complex, involving key residues such as Tyr70, Asp72, Trp84, Tyr121, Trp279, and Phe330.