Homology Modeling And Docking Of Inhibitory Glutamate Receptors

Inhibitory glutamate receptors(IGluRs)are ligand-gated ion channel protein currently which only present in invertebrates,also known as glutamate-gated chloride channels(GluCl).In the presence of glutamate,it will open the chloride channel.Due to it is currently only found in invertebrates,GluCl thus conducive to the development of high efficiency and high-selective insecticides.Avermectins are bio-fermentation products and their derivatives of high efficiency,low toxicity,broad insecticidal spectrum,high safety to mammalian and low residual to environment.Studies have shown that GluCl is the main target of avermectins.To explore the action mechanism between avermectins and GluCl and develop higher activity and more selective avermectin insecticides,in the dissertation,GluCl structure of Tetranychus urticae Koch and Plutella xylostella are constructed by homology modeling with a template of Caenorhabditis elegans GluCl and then docked with Avermectins.The main research contents are as follows:1.Avermectins(AVM?IVM?EMA)are docked with Caenorhabditis elegans GluCl,the results indicate that avermectins focus on the interspace between TM1 and TM3 of adjacent subunits nearby outer membrane region.The disaccharide of avermectins are deeply embedded into this void.Strong hydrophobic interaction,hydrogen bonding interaction,super conjugation effect and Van der Waals' force are generated between disaccharide and the surrounding amino acid residues.The other parts of avermectins can not be thoroughly embedded for steric hindrance and rigidity.Accumulation effect and super conjugation effect are generated between the parts and the surrounding amino acid residues.2.Tetranychus urticae Koch GluCl is constructed by homology modeling with a template of Caenorhabditis elegans GluCl.After being checked,the results of dynamics simulation and conformational analyses shows the modeling structure is reasonable.Avermectins(AVM?IVM?EMA)are docked with Tetranychus urticae Koch GluCl,the results indicate that avermectins focus on the interspace between TM1 and TM3 of adjacent subunits nearby outer membrane region.The disaccharideof avermectins are deeply embedded into this void.Strong hydrophobic interaction,hydrogen bonding interaction,super conjugation effect and Van der Waals' force are generated between disaccharide and the surrounding amino acid residues.The other parts of avermectins can not be thoroughly embedded for steric hindrance and rigidity.Accumulation effect and super conjugation effect are generated between the parts and the surrounding amino acid residues.3.Plutella xylostella GluCl is constructed by homology modeling with a template of Caenorhabditis elegans GluCl.After being checked,the results of dynamics simulation and conformational analyses shows the modeling structure is reasonable.Avermectins(AVM?IVM?EMA)and other 4 designed compounds are docked with Tetranychus urticae Koch GluCl,the results are similar with the previous and it is in agreement with measured biological activity of Plutella xylostella.The results indicate that disaccharide is crucial for avermectins biological activity.