title: Molecular modeling of sulfoxaflor and neonicotinoid binding in insect nicotinic acetylcholine receptors: impact of the Myzus β1 R81T mutation.
abstract: BACKGROUND
  Sulfoxaflor (Isoclast™ active), a new sulfoximine-class insecticide, targets sap-feeding insect pests, including those resistant to neonicotinoids. Sulfoxaflor acts on the insect nicotinic acetylcholine receptor (nAChR) in a distinct manner relative to neonicotinoids. Unlike any of the neonicotinoids, sulfoxaflor has four stereoisomers. A homology model of Myzus persicae (green peach aphid) based on the ACh binding protein from Aplysia californica, overlaid with M. persicae nAChR sequence (α2 and β1 subunits) was used to investigate the interactions of the sulfoxaflor stereoisomers with WT and R81T versions of the nAChR.
  
  
  RESULTS
  Whole-molecule van der Waals interactions are highly correlated with the binding affinity for the neonicotinoids and correctly predict the rank order of binding affinity for neonicotinoids and sulfoxaflor. The R81T mutation in M. persicae nAChR is predicted to have much less effect on binding of sulfoxaflor's stereoisomers than that of the neonicotinoids.
  
  
  CONCLUSIONS
  All four stereoisomers predictably contribute to the activity of sulfoxaflor. The WT and R81T nAChR homology models suggest that changes in a whole-molecule electrostatic energy component can potentially explain the effects of this target-site mutation on the pattern of reduced efficacy for the modeled neonicotinoids, and provide a basis for the reduced effect of this mutation on sulfoxaflor. © 2016 Society of Chemical Industry.
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Nick X
authors.initials: NX
authors.lastname: Wang
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Watson
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loso
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Sparks
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects / Q000235:genetics*; D001665:Binding Sites; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics*; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D007306:Insecticides; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D013457:Sulfur Compounds; C560328:sulfoxaflor
keywords: nAChR modeling; neonicotinoid target-site resistance; nicotinic acetylcholine receptor; sulfoxaflor; sulfoximine insecticide