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Organophosphate (OP) poisoning induces inhibition of acetylcholinesterase (AChE) thereby accumulation of a neurotransmitter acetylcholine in synaptic gap. Simulated binding of OPs with human AChE was performed to study mechanistic insight of binding and inhibition. High precision flexible ligand docking of seventy-five OPs with human AChE enzyme (HuAChE) individually reveals binding energies of OPs; lowest in Pyraclofos followed by Phenthoate acid, Prothiophos, Methyl isofenphos, Sulprophosoxon and Propaphos. Aromatic amino acids such as Trp86, Phe295, Arg296, Tyr337, Phe338, Tyr341 etc were noticed in Pi interactions due to partial negative charges on surface of aromatic group. Pi-cation interactions were most favored by OPs and were contributed by Trp86 due to presence of anionic indole ring. Although Phe295, Phe298 and Tyr341 were also involved in Pi-sigma or Pi-Pi interactions, Trp86 played a key role in amino acid stabilizing OP-HuAChE complex by Pi-cation interaction. Study suggested that amino acid Trp86 has provided a most potent Pi-cation binding site. Trp86 along with other aromatic residues played crucial role in stabilizing organophosphate-human acetylcholinesterase complex thereby inhibition of target enzyme.

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