Molecular docking and interaction of natural aroma compounds on acetylcholinesterases: Insights of in-silico perspective on stored grain insect pests

Abstract

Current mitigation approaches for stored grain insect pests involve the use of synthetic pesticides and fumigants. These control measures although effective, frequently lead to ecological contaminations and growing resistance among insect pest populations. There is also a need for developing targeted pesticides, necessary for minimizing cross species contamination. In this context, the current study investigates acetylcholinesterase (AChE), a key enzyme in insect neurotransmission, as a target to examine phytochemical-based compounds (from Mentha and Ocimum species) that do not target human AChE system. Through multiple sequence alignment of test organisms' AChE FASTA sequences, the study identified conserved catalytic triads (serine, histidine and glutamic acid) and insect specific peripheral entrance site residues such as Leucine (in Sitophilus oryzae, Tribolium castaneum, Oryzaephillus surinamensis, Callosobruchus maculatus) and Cysteine (in Rhyzopertha dominica, Lasioderma serricorne, Stegobium paniceum) within AChE active gorge. This distinction at entrance site residues was further supported by phylogenetic analysis, indicating a potential for selective intervention. To validate this prospect, molecular docking was performed to assess the interaction of selected phytochemical compounds with identified entrance and catalytic site residues of pests’ AChE enzymes. Although standard inhibitors (donepezil and physostigmine) showed higher docking scores ranging from −10 to −4.3 kcal/mol, plant derived compounds exhibited prominent compound-specific and insect-specific binding affinities. Menthol and p-allylanisole were ADMET profiled and identified as key compounds to reduce off target toxicity as they specifically targeted pest species AChE system. These computational insights highlight the potential of phytochemicals as sustainable alternatives for alleviating stored grains insect pests.