title: Predictive 3D modelling of the interactions of pyrethroids with the voltage-gated sodium channels of ticks and mites.
abstract: BACKGROUND
  The pyrethroid insecticides are a very successful group of compounds that target invertebrate voltage-gated sodium channels and are widely used in the control of insects, ticks and mites. It is well established that some pyrethroids are good insecticides whereas others are more effective as acaricides. This species specificity is advantageous for controlling particular pest(s) in the presence of another non-target invertebrate, for example controlling the Varroa mite in honeybee colonies.
  
  
  RESULTS
  We applied in silico techniques to compare the voltage-gated sodium channels of insects versus ticks and mites and their interactions with a range of pyrethroids and DDT analogues. We identified a single amino acid difference within the pyrethroid binding pocket of ticks/mites that may have significant impact on the effectiveness of pyrethroids as acaricides. Other individual amino acid differences within the binding pocket in distinct tick and mite species may provide a basis for future acaricidal selectivity.
  
  
  CONCLUSIONS
  Three-dimensional modelling of the pyrethroid/DDT receptor site has led to a new hypothesis to explain the preferential binding of acaricidal pyrethroids to the sodium channels of ticks/mites. This is important for understanding pyrethroid selectivity and the potential effects of mutations that can give rise to resistance to pyrethroids in commercially-important pest species.
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bavaria, Germany.
authors.forename: Andrias O
authors.initials: AO
authors.lastname: O'Reilly
authors.forename: Martin S
authors.initials: MS
authors.lastname: Williamson
authors.forename: Joel
authors.initials: J
authors.lastname: González-Cabrera
authors.forename: Andreas
authors.initials: A
authors.lastname: Turberg
authors.forename: Linda M
authors.initials: LM
authors.lastname: Field
authors.forename: B A
authors.initials: BA
authors.lastname: Wallace
authors.forename: T G Emyr
authors.initials: TG
authors.lastname: Davies
mesh_terms: D056810:Acaricides / Q000494:pharmacology*; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D021621:Imaging, Three-Dimensional; D008925:Mites / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011722:Pyrethrins / Q000737:chemistry* / Q000378:metabolism; D013987:Ticks / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D056810:Acaricides; D060829:Arthropod Proteins; D011722:Pyrethrins; D061566:Voltage-Gated Sodium Channels
keywords: DDT; acaricides; mites; pyrethroids; resistance; ticks; voltage-gated sodium channel