Study On Homology Modeling And Molecular Docking Of The Common Natural Products Targeting Cannabinoid Receptor CB2

Background: Computer Aided Drug Design(CADD)is becoming an important tool in the development of modern medicine.It has been widely used in drug design research because of its low cost,high efficiency and high accuracy.It plays an increasingly important role in the discovery and optimization of lead compounds.The current study shows that cannabinoid receptor is a very important drug target,It has two receptor subtypes CB1 and CB2,Drug targets in the CB1 receptor has a good analgesic effect in clinical applications,but it is easy to addiction,caused a series of central nervous side effects.Drug targets in the CB2 receptor agonist not only has a good analgesic effect,but also does not produce dependence,addiction and other central side effects.Therefore,the study of CB2 receptor as the target of the drug has a better clinical prospects.Objective: Based on the crystal structure of CB1 receptor,the crystal structure of cannabinoid receptor CB2 was constructed by homology modeling.Based on the common small molecule library of 1000 Chinese medicine,small molecule compounds with chitosan receptor CB2 agonism were selected by molecular docking,And then tested their pharmacological activity in the laboratory.In order to developed new drug of CB2 receptor agonists.Method: First,According to the known CB1 receptor protein crystal structure,the protein crystal structure of CB2 receptor was constructed by homology modelingelimination reaction.Second,Based on the common small molecule library of1000 Chinese medicine,the molecular docking method was used to screen the small molecule compound with the action of cannabinoid receptor CB2.Third,The pharmacokinetic activity of the small molecule compounds screened by laboratory tests on the production of cAMP in HEK 293 cells was tested.Result and Conclusion: According to the results of molecular docking,six compounds with possible CB2 receptor agonist activity were screened out,The resultsshow that Calceolarioside B and SibiricoseA6 have a high fluorescence inhibition rate,which indicates that these two compounds have a good activity for CB2 receptors.