Homology Modeling And Docking Of Guanosine Binding Protein Coupled Receptors

Guanosine binding Protein Coupled Receptors(GPCRs), as the biggest receptor super family, control various signal transduction pathways by the member of GPCRs. The research about how they guiding the a variety of biological effects becomes very meaningful. Ryanodine Receptor(Ry R), one of the GPCRs super family, is a vital insecticide target due to it’s widely distributing in the lepidoptera insect. The ryanodine receptor also exists in mammals, but the safety of the ryanodine receptor insecticides to mammals is not clear. In order to discuss the mechanism of ryanodine receptor insecticides, three-dimensional structure of Human Ryanodine Receptor 2 was built by homology modeling in this study. It’s great help to explore more safety and better selectivity ryanodine receptor insecticides. Thirty-three phthalic diamide compounds were docked into Heliothis Virescens Ryanodine Receptor and Human Ryanodine Receptor 2, then we learnt the differences of their mechanisms by the scoring function.The main study is as follows:1. Three-dimensional model of Heliothis Virescens Ryanodine Receptor was built by Human Ryanodine Receptor 2 as the model. Using dynamics simulation study and Ramachandran to analysis the stable and reasonable of the Heliothis Virescens Ryanodine Receptor model.2. Thirty-three phthalic diamide compounds were docked into Heliothis Virescens Ryanodine Receptor, it matched well between the scoring function and biological activity, which also a strong evidence to prove the reasonable of Heliothis Virescens Ryanodine Receptor model. The great difference between high scoring compounds and low scoring compounds was found by further research. As the stronger π-π stacking interaction and hydrogen bonding interaction, the compounds which acquire pyridine ring got higher docking score. The important role of pyridine ring also reminded us to design new phthalic diamide compounds.3. Thirty-three phthalic diamide compounds were docked into Human Ryanodine Receptor 2, It shown no obvious differences about the total score. The π-π stacking interaction and hydrogen bonding interaction between phthalic diamide compounds and Human Ryanodine Receptor 2 were extremely weak.The results provided theoretical basis for developing ryanodine receptor insecticides.