In Silico modeling of voltage-gated sodium channel alpha subunit to understand insecticide binding simulation in mosquitoes

The Voltage Gated Sodium Channel (VGSC) is critical for binding of different insecticides and play key role in insecticide resistance. An important mechanism of resistance to DDT and pyrethroids is termed knockdown resistance (kdr), caused by mutations in IIS6 domain of sodium channels. To attain a better management strategy for insecticide resistance and screening of new insecticide molecules, it is important to understand the three-dimensional structure of insecticide-binding domain of VGSC and its molecular interaction with insecticides. We constructed a theoretical model of ion transport domain–II of VGSC from mosquitoes, Culex quinquefasciatus . The stereochemistry of the model shows 91.1% residues are in the most favored region. Docking studies with DDT and deltamethrin indicated that deltamethrin showed interaction with Thr 929 , Met 918 , Ile 936 , Cys 933 , Leu 925 , Glu 881 , Met 857 and Gly 866 and DDT showed interaction with Ile 936 , Thr 929 , Ser 878 , Phe 863 , Gln 864 , Trp 861 and Met 857 . We also predicted that mutation of Thr 929 should confer resistance to both DDT and deltamethrin.