Starting with the nicotine-nicotinic acetylcholine receptor (nACHR) complex crystal structure, the precise model for three kinds of neonicotinoids: imidacloprid, thiacloprid and nitenpyram and also three imidacloprid derivatives acting with the receptor protein was investigated by the FlexX molecular docking model of the SYBYL 6.92 software package. The conformation library constructed by a system search method was used in docking. The results were filtered according to the clustering by comparing the RMS of the conformations and the data of CScore evaluation function. Finally an appropriate neonicotinoid-nACHR pharmacophoric conformation model was given in which the nitrogen in the pyridine ring of a ligand generates a hydrogen bond with the LEU102, MET114 residues in a receptor through a water molecule and the hydrophilic side chain on the imidazole or thiazole ring of the ligand generates a hydrogen bond with the CYS187 or SER186 residues in the receptor and also the hydrophobic side chain acts with the hydrophobic pocket A (TYR164, TRP53, TYR89 and TYR185) or the other hydrophobic pocket B (TYR132, CYS187 and CYS188). This model consists with the experiment result in the earlier reference so that the validity is strongly proved. According to the conformation model some suggestions about how the structures can be modified to improve the activity and some clues to the reason for their high selectivity were also given.

Key words: neonicotinoid, molecular docking, FlexX