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《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

Issue:

2018年03期

Page:

85-

Research Field:

·生命科学·

Publishing date:

Info

Title:

Study on the Molecular Targeting Docking Virtual Screening ofPotential Active Components in Tong-Xie-Yao-Fang

Author(s):

Li Xiaoran; Yang Xinghao

School of Life Sciences,Nanjing Normal University,New Drug Research Center,Nanjing 210023,China

Keywords:

Tong-Xie-Yao-Fang; targeting docking; irritable bowel syndrome

PACS:

R285

DOI:

10.3969/j.issn.1001-4616.2018.03.014

Abstract:

This study was based on a novel drug target of irritable bowel syndrome(IBS)and used molecular targeted docking technology to virtually screen promising natural small molecules from Tong-Xie-Yao-Fang. The active compound database of Tong-Xie-Yao-Fang was created,which contained a total of 239 compounds. And four proteins were selected as the targets including Tryptophan Hydroxylase 1(TPH₁),Serotonin Transporter(SERT),Corticotropin Releasing Factor Receptor 1(CRFR₁),and Transient Receptor Potential Vanilloid Receptor 1(TRPV₁). The whole process covers the ligands database construction,receptor protein preparation,docking site study,docking parameter setting,molecular docking batch scoring,binding mode analysis,interaction analysis,and pharmacophore analysis virtual screening process. The results showed that 123 of the natural compounds docked with the receptor scored the first 30% showing good ligand-receptor interaction,they present the characteristics of "single target,multiple ligands". This study also found that Paeoniflorin in the Paeoniae Radix Alba,Deltoin in the Radix Saposhnikoviae Divaricatae,Naringin in the Pericarpium Citri Reticulatae,and β-Vatirenene in the Atractylodes Macrocephala have the most“single component,multiple targets”therapeutic potential. The results showed that 13 compounds including 4-O-methyl-paeoniflorin,iso-Paeoniflorin and Gallotannin; iso-Benzoylpaeoniflorin,iso-Paeoniflorin and Benzoylpaeoniflorin; Paeoniflorin,Albiflorin R₁and Albiflorin; Deltoin,Galloylpaeoniflorin,Galloylpaeoniflorine and Benzoylpaeoniflorin were the most promising natural compounds. The pharmacophore model analysis showed that the TPH₁ ligand contained two hydrogen bond acceptors and three hydrogen bond donors. The SERT ligand contained four hydrogen bond acceptors,two hydrogen bond donors and one hydrophobic center. CRFR₁ contained one hydrogen bond acceptor,two hydrogen bond donors and one hydrophobic center. TRPV₁ contained three hydrogen bond acceptors and one hydrophobic center. 12 potential compounds were achieved through the screening process above. This study provides candidate compounds for the development of IBS therapeutic drugs and reference for exploring the molecular mechanism of Tong-Xie-Yao-Fang.

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Last Update: 2018-11-19