Volume 20, Issue 45, January - June, 2026

Molecular docking study for the interaction behavior of human acetylcholinesterase catalytic activity with common organophosphate pesticides

Hala A Abdelgaid¹, Khairy A Ibrahim^2♦

¹Egyptian Center for Disease Control (CDC), National Hepatology and Tropical Medicine Research Institute (NHTMRI), Corniche El Nil - Imbaba – Giza, P.O. BOX 12651, Egypt.
²Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza, 12618, Egypt.

^♦Corresponding Author
Khairy A. Ibrahim, Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza, 12618, Egypt.

ABSTRACT

Organophosphate pesticides (OPs) are the most commonly used pesticides and act as key inhibitors of acetylcholinesterase (AChE). However, their mechanism of action in human AChE (hAChE) is not well studied. The recent release of new 3D structures of hAChE in the NCBI database prompted us to investigate their interactions with the enzyme's catalytic active site. We used an in silico molecular docking approach with AutoDock Vina to study the interactions of thirty common OPs with a new hAChE structure (6WUZ). The binding energies of the lowest-energy poses were determined to select conformers for further analysis. Based on interactions with Ser203 and His447, our study divided the OPs into three groups of hAChE inhibitors. The first group comprised eight OPs that interacted with both Ser203 and His447 at the catalytic active site, suggesting strong inhibition with docking energy ranging from −7.6 to −5.1 kcal/mol. The second group comprised nine compounds that did not interact with Ser203 but interacted with His447, suggesting medium inhibition with docking energy ranging from −7.9 to −5.2 kcal/mol. The third group comprised thirteen compounds that did not interact with either His447 or Ser203, with docking energy ranging from −7.5 to −4.5 kcal/mol, and were expected to be weak hAChE inhibitors. In conclusion, the studied OPs exhibit distinct interaction behaviors with hAChE, which may help us understand their toxicity and inform the development of new strategies for AChE reactivators after OP exposure and for the treatment of neurodegenerative disorders.

Keywords: Organophosphates, Human Acetylcholinesterase, Active Site, Autodock Vina, Free Energy

Drug Discovery, 2026, 20(45), e7dd3053

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Published: 27 February 2026