Virtual Screening Study Of The Active Ingredients Of Tongxie Yaofang Based On Targets Related To Irritable Bowel Syndrome

Objective:The computer virtual screening technology was used to search for compounds with potential therapeutic potential for the treatment of irritable bowel syndrome from the compounds contained in the prescription,which lay the foundation for clarifying the mechanism of action.Method:The use of traditional Chinese medicine database(TCM database@Taiwan)construction of Tong-Xie-Yao-Fang formula compounds database,containing a total of 239 candidate compounds with Tryptophan hydroxylase 1(TPH1),Serotonin Transporter(SERT),Corticotropin releasing factor receptor 1(CRFR1)and Transient receptor potential vanilloid receptor 1(TRPV1)four receptors as the targets for irritable bowel syndrome related therapeutic targets,using molecular docking program-AutoDock Vina to study the interaction between target proteins and compounds from Tong-Xie-Yao-Fang formula.The binding modes and interactions of the optimal ligand of each receptor’s score results are analyzed by Discovery Studio and MOE software.Then,using the Discovery Studio to construct the pharmacophore model of the top five ligands of each receptor and summarize the commonality of the structures.Next,applying the Cytoscape software for network analysis of the scoring results and data mining.Results:The results of the binding scores of 239 compounds were ranked based on their Gibbs free energy,and 33 natural compounds have the binding potential for four proteins,which account for 13.8%of the Tong-Xie-Yao-Fang database.For the ligand of TPH1,the pharmacophore model contains two hydrogen bond receptors and three hydrogen bond donors while the SERT has four hydrogen bond receptors,two hydrogen donors and one hydrophobic center.The pharmacophore model of CRFR1 includes one hydrogen donor,two hydrogen donors and one hydrophobic center while TRPV1 contains three hydrogen bond receptors and one hydrophobic center.There are 81 compounds could bind to two or more receptors.58 compounds have the potential for binding to three or more proteins.Moreover,33 compounds can interact with all four receptors.Conclusion:The compounds of the Tong-Xie-Yao-Fang can interact with four receptor targets.According to the study,it provides the reference for design and research of IBS-related targets on natural medicine.At the same time,it contributes to the interpretation of the mechanism of Tong-Xie-Yao-Fang in the micro molecular level.