title: Insight into the Meligethes aeneus voltage-sensitive sodium channel structure and an attempt to select the best pyrethroid ligands.
abstract: BACKGROUND
  The voltage-sensitive sodium channel (VSSC) is a target for the pharmacological action of pyrethroids which are used in controlling pests, including those of agricultural importance. Among these is the pollen beetle (Meligethes aeneus F.) - the most serious pest of Brassica napus. Owing to the heavy use of pyrethroids, a widespread build-up of resistance has occurred. The main cause of pyrethroid insensitivity in M. aeneus is considered to be an increased oxidative metabolism; however, the additional mechanism of resistance associated with mutations in the VSSC might contribute to this phenomenon.
  
  
  RESULTS
  We generated a VSSC 3D model to study the docking affinities of pyrethroids to their target site within the channel. Our goal was to identify the pyrethroids for which docking affinity scores were high and not affected by potential mutations in the VSSC. We found that the docking scores of cypermethrin are hardly influenced by the appearance of point mutations. Additionally, tau-fluvalinate, deltamethrin and bifenthrin are VSSC ligands with high affinity scores.
  
  
  CONCLUSIONS
  Our docking models suggest that point mutations in the VSSC binding pocket might affect the stability of ligand interactions and change the pattern of ligand docking locations, which might have a potential effect on VSSC gating properties.
authors: Interdepartmental Laboratory of Molecular Biology, Institute of Plant Protection - National Research Institute, Poznań, Poland.
authors: Aleksandra
authors: A
authors: Obrępalska-Stęplowska
authors: Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznań, Poland.
authors: Anna
authors: A
authors: Czerwoniec
authors: Interdepartmental Laboratory of Molecular Biology, Institute of Plant Protection - National Research Institute, Poznań, Poland.
authors: Przemysław
authors: P
authors: Wieczorek
authors: Interdepartmental Laboratory of Molecular Biology, Institute of Plant Protection - National Research Institute, Poznań, Poland.
authors: Barbara
authors: B
authors: Wrzesińska
mesh_terms: D000818:Animals; D001517:Coleoptera / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011722:Pyrethrins / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000235:genetics
chemical_list: D019476:Insect Proteins; D008024:Ligands; D011722:Pyrethrins; D061566:Voltage-Gated Sodium Channels
keywords: 3D structure; insecticide resistance; insects; mutations; pollen beetle (Meligethes aeneus F.); protein-ligand interactions; pyrethroids; three-dimensional model; voltage-sensitive sodium channel