Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking

Yan LI; Ya-li LUO; Yong-qi LIU; Cai-qin FENG; Xiao-jie JIN; Yong-chang ZHU

doi:10.13422/j.cnki.syfjx.20191704

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Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking

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- Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 17, Pages: 173-180(2019)
- 作者机构：
  
  1.甘肃中医药大学　甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室，兰州　 730000；
  2.甘肃中医药大学　敦煌医学与转化省部共建教育部重点实验室，兰州　 730000；
  3.甘肃中医药大学　药学院，兰州　 730000；
  4.兰州大学　应用有机化学国家重点实验室，兰州　 730000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191704
  CLC： R2-0; R22; R285.5; R289
- Received：03 January 2019，
  
  Published Online：21 May 2019，
  
  Published：05 September 2019
- 稿件说明：
移动端阅览
Yan LI, Ya-li LUO, Yong-qi LIU, et al. Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 173-180.
DOI：

Yan LI, Ya-li LUO, Yong-qi LIU, et al. Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 173-180. DOI： 10.13422/j.cnki.syfjx.20191704.

摘要

目的：

基于分子对接的方法研究拮抗肿瘤坏死因子受体1(TNFR1)的红芪小分子化合物。

方法：

从相关中药化学成分化合物库下载红芪小分子化合物结构，进行结构优化，获得红芪成分化合物库；确定炎症靶点TNFR1三维结构(PDB ID：1TNR)，进行加氢、去水等处理，根据文献确定结合口袋残基；根据确定的靶点结构和结合口袋，将成分化合物库与靶点进行柔性分子对接，获得打分值(Glide Score)；基于分子对接结果，选择Glide Score前9个小分子化合物为候选成分，在此基础上进行类药性分析，即符合氢键受体数、氢键供体数量、分子量、可旋转键的数量、脂水分配系数的数值范围的小分子化合物；最后根据药代动力学参数及成分-靶点对接的复合物结构进行结合模式分析。

结果：

确定TNFR1药物结合口袋的残基组成为谷氨酸109(Glu109)，赖氨酸35(Lys35)，丙氨酸62(Ala62)，丝氨酸74(Ser74)，赖氨酸75(Lys75)，半胱氨酸76(Cys76)，精氨酸77(Arg77)，谷氨酸82(Gln82)，苏氨酸89(Thr89)，天冬氨酸91(Asp91)，精氨酸92(Arg92)，天冬氨酸93(Asp93)，苏氨酸94(Thr94)，缬氨酸95(Val95)，半胱氨酸96(Cys96)，精氨酸104(Arg104)，酪氨酸106(Tyr106)，天冬酰胺110(Asn110)，亮氨酸111(Leu111)，苯丙氨酸112(Phe112)，谷氨酸131(Glu131)，赖氨酸132(Lys132)；检索得到红芪43个小分子化合物；以对接打分等综合筛选出槲皮素、异甘草素、柚皮素、毛蕊异黄酮及甘草素5个红芪小分子化合物。

结论：

红芪抗炎的有效物质基础槲皮素、异甘草素、柚皮素、毛蕊异黄酮及甘草素具有成为TNFR1拮抗剂的较大可能性。

Abstract

Objective:

To study the effect of small molecule compounds of Hedysari Radix in ntagonizing tumor necrosis factor receptor type 1 (TNFR1) based on molecular docking.

Method:

The structure of small molecular compound of Hedysari Radix was downloaded from the chemical composition compound library of traditional Chinese medicine

and then optimized to obtain the composition compound library of Hedysari Radix. The three-dimensional structure of the inflammatory target TNFR1 (PDB ID: 1TNR) was identified. After hydrotreating and anhydrating

the binding pocket residues were identified according to the literature. According to the defined target structure and binding pocket

the flexible molecular docking was conducted between the composition compound library and the target

and the score (Glide Score) was obtained. Based on the results of molecular docking

the first nine small molecular compounds of Glide Score were selected as candidate components. On this basis

the drug-likeness was analyzed

which involved small molecular compounds that meet the number of hydrogen-bonded receptors

the number of hydrogen-bonded donors

the formula weight

the number of rotatable key and the numerical range of lipo-hydro partition coefficient. Finally

the binding mode was analyzed according to pharmacokinetic parameters and complex structure of composition-target docking.

Result:

The residue set in the TNFR1 drug-binding pocket were identified as glutamic acid109 (Glu109)

lysine 35(Lys35)

alanine62 (Ala62)

serine 74 (Ser74)

lysine75 (Lys75)

cysteine76 (Cys76)

argnine 77(Arg77)

glutamine82 (Gln82)

threonine89 (Thr89)

asparticacid91 (Asp91)

argnine92 (Arg92)

aspartic acid93 (Asp93)

threonine 94(Thr94)

valine95 (Val95)

cysteine 96(Cys96)

argnine104 (Arg104)

tyrosine106 (Tyr106)

asparagine110 (Asn110)

leucine111 (Leu111)

phenylalanine112(Phe112)

glutamic acid 131(Glu131) and lysine132 (Lys132). Totally 43 small molecular compounds of Hedysari Radix were obtained. Five small molecular compounds

namely hedysari radix

quercetin

isoliquiritin

naringenin

calycosin and liquiritigenin

were screened by comprehensive factors

like docking scoring.

Conclusion:

Quercetin

isoliquiritin

naringenin

calycosin and liquiritigenin are the effective anti-inflammatory substances of Hedysari Radix

with a great possibility of becoming TNFR1 antagonists.

关键词

Keywords

references

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