Gossypium spp., produces economically important cotton fiber, and its yield is highly affected due to pest attacks. Insecticidal target site mutation is one of the reasons behind insecticide resistance to a wide range of pesticides. Acetylcholinesterase (AChE) protein sequences from major pests of cotton were analyzed to assess various physicochemical properties, presence of motifs, and understand evolutionary relationship. The impact of three mutant AChE1, A. lucorum A216S, B. tabaci F392W, and A. gossypii A302S, on the strucutral stability was assessed, and F392W_AChE1 was selected based on 100 ns molecular dynamics simulation. Virtual screening of the zinc database and high-throughput virtual screening, standard precision, and extra precision docking resulted in the identification of six compounds. The six identified compounds and six known commercial pesticdes were docked with three mutant and three wild type AChE1, and one (C1) was selected based on Tice criteria. The conformational and interaction stability of the AChE1-C1 and F392W_AChE1-C1 complexes were monitored at 100 ns Gromacs simulation and were found to be thermodynamically favorable. Therefore, C1 may have the potential to bind to the resistant and susceptible strains of cotton pest, and the resistance developed by insects could be arrested. Furthermore, synthesis and field study of C1 will lead us to a better understanding of the efficacy of the identified compound.
© 2022 The Authors. Published by American Chemical Society.