Abstract
Binding-site interactions of nicotinic insecticides have been defined by comparative chemical and structural biology approaches using mollusk acetylcholine binding proteins which serve as structural surrogates of the insect and vertebrate nicotinic acetylcholine receptor (nAChR) subtypes. Neonicotinoids with an electronegative pharmacophore are embraced by a reversed position in the binding pocket compared with a nicotinoid cationic functionality. A single dominant binding orientation causes high affinity for neonicotinoids at the insect nAChR homologue. However, the inferior potency of neonicotinoids at the vertebrate nAChR model is associated with multiple binding conformations rivaling in the agonist-binding pocket. These findings in molecular recognition conferring potency and selectivity facilitated illustrative studies on nAChR structure-guided insecticide design.
