IN-SILICO STUDY OF ACETYLCHOLINESTERASE INHIBITION BY ORGANOPHOSPHATE PESTICIDES

Abstract

Pesticides are widely used round the globe for a plethora of applications that vastly
includes agricultural fields and commercial gardens. Despite their wide use that aid
increase in crop yield, they have ill-effects on environment and non-target organisms.
Organophosphates (OP) are an important class of pesticides, which cause irreversible
inhibition of acetylcholinesterase (AChE). Irreversible inhibition of AChE may lead to
severe pathological conditions such as muscular paralysis, bronchial constriction and
even death by asphyxiation. An in-silico approach was employed to study the interaction
of AChE with four commonly used OP pesticides namely, methyl parathion, dichlorvos,
malathion, chlorpyrifos. AutoDock4.2 and iGEMDOCK and SwissDock are opensource
docking tools which were used to form the AChE-OP complex. Further these complexes
were explored on their protein-ligand binding affinity along with the mechanism of
binding. Based on the results, It was found that chlorpyrifos has the best binding affinity
with AChE as compared to the other pesticides. These observation would surely be
helpful in development of precautionary antidotes for the people who have direct contact
with these poisonous pesticides. In addition, this information may be utilized in
developing non-toxic therapeutic leads from the best binding pesticides, for Alzheimer’s
diseases, where AChE is considered as a potential drug target.