title: Actions between neonicotinoids and key residues of insect nAChR based on an ab initio quantum chemistry study: hydrogen bonding and cooperative pi-pi interaction.
abstract: Neonicotinoid insecticides show selective actions on insect nicotinic acetylcholine receptor (nAChR). Two key residues (Trp and Arg/Lys) have been identified as contributing to the neonicotinois binding. To investigate the selective mechanism, a computational model was set up to simulate the interaction between residues (Trp and Arg) of insect nAChR and neonicotinoids by quantum chemistry method. Three analogues of neonicotinoid derivatives without the chloropyridinyl moiety and 3-methyl-indole (3MI), guanidinium (Gua) were used to mimic the neonicotinoids and the side chain of key residues Trp and Arg accordingly. Interaction features of 3MI-analogues, analogues-Gua and 3MI-analogues -Gua complexes were analyzed comparatively. Hydrogen bonding between the nitro group of analogues and Gua was found to be the most important for binding. Moreover, the cooperative pi-pi interaction between analogues and the indole ring, which is strengthened by the existence of Gua, also contributes to the binding. The alternative binding model of neonicotinoids proposed here, although slightly different from others, might be close to the actual.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiagao
authors.initials: J
authors.lastname: Cheng
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry; D007313:Insecta; D008958:Models, Molecular; D018716:Molecular Mimicry; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009574:Nitro Compounds / Q000737:chemistry; D011789:Quantum Theory; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; D009538:Nicotine