title: In Silico analysis of voltage-gated sodium channel in relation to DDT resistance in vector mosquitoes.
abstract: The voltage-gated sodium channel (VGSC) is the target site for insecticides such as DDT and synthetic pyrethroids. A single base (A-T) change in the knock-down resistance (kdr) allele leads to an amino acid substitution at position 267 that confers the target-mediated resistance to DDT and synthetic pyrethroids in Anopheles gambiae. A theoretical model of the VGSC domain II that contains the site of mutation was constructed using the K;+ channel protein of Aeropyrum pernix as a template. The validated model with 88.6% residues in the favored region was subjected to the CASTp program that predicted 30 pockets in the modeled domain II for ligand interaction. In the model, at position 267, leucine was manually replaced with phenylalanine. When this altered model was subjected to the CASTp program, the search results showed the same number of pockets. The docking results indicate that DDT interacts with the modeled VGSC domain II at position 275 in the presence of leucine or in the presence of phenylalanine (binding energy =-5.32 kcal/mol, -6.21 kcal/mol). It appears from the results that the mutation at position 267 has no direct influence on the interaction of DDT with the target protein. Therefore, to understand the interaction affinity of DDT with the target and influence of the mutation on the existence of active sites/pockets in relation to ligand binding, a whole VGSC model is necessary.
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur - 613 402, India.
authors.forename: Rengaraj
authors.initials: R
authors.lastname: Rajesh
authors.forename: Kasinathan
authors.initials: K
authors.lastname: Gunasekaran
authors.forename: Subramanian
authors.initials: S
authors.lastname: Muthukumaravel
authors.forename: Kothandapani
authors.initials: K
authors.lastname: Balaraman
authors.forename: Purusothaman
authors.initials: P
authors.lastname: Jambulingam
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D009033:Culicidae; D003634:DDT / Q000494:pharmacology*; D007305:Insecticide Resistance; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics
chemical_list: D015222:Sodium Channels; D003634:DDT