天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (3): 484-490.doi: 10.16333/j.1001-6880.2022.3.016

• 数据研究 • 上一篇    下一篇

基于TCMSP数据库的分子对接虚拟筛选JAK3特异性抑制剂

万祥宏，蔡沐彬，游清徽*   

  1. 江西师范大学生命科学学院，南昌 330022
  • 出版日期:2022-03-28 发布日期:2022-03-29
  • 基金资助:
    国家科技重大专项子课题（2018ZX09721002-008）；江西师范大学教学改革研究课题（JXSDJG16078）

Virtual screening of JAK3 specific inhibitors using molecular docking based on TCMSP database

WAN Xiang-hong,CAI Mu-bin,YOU Qing-hui*   

  1. College of Life Sciences,Jiangxi Normal University,Nanchang 330022,China
  • Online:2022-03-28 Published:2022-03-29

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摘要： 以LeDock分子对接软件对TCMSP数据库中的13 445种中草药成分小分子与JAK3激酶进行分子模拟对接研究，分析对接结合自由能与配体效率，筛选出18种小分子，再根据受体与配体的相互作用进一步分析，得到7种与JAK3激酶有较好结合作用的小分子，并且发现JAK3激酶分子中氨基酸残基Arg953、Asp967、Lys830、Ala966和Asn954是小分子与酶形成氢键作用的重要位点，为JAK3抑制剂的开发设计提供有力依据。以其他JAK家族成员为靶蛋白，进行反向筛选，发现断马钱子苷（scologanin）对JAK3激酶表现出强结合力与高选择性。本研究意在寻找可以作为JAK3激酶高选择性抑制剂的中草药药效小分子，结果发现断马钱子苷具备相应的潜力，值得进一步深入研究。

关键词: JAK激酶, 抑制剂, 分子对接, TCMSP数据库

Abstract:

LeDock molecular docking software was used to simulate the docking of 13 445 small molecules of Chinese herbal components in the TCMSP database with JAK3 kinase.According to the analysis of docking binding free energy and ligand efficiency,18 molecules were screened out,and then further analyzed according to the interaction between receptor and ligand,7 molecules having better binding with JAK3 kinase were found.The amino acid residues Arg953,Asp967,Lys830,ALA966 and Asn954 in JAK3 kinase molecule were important sites for the formation of hydrogen bond between small molecules and JAK3 kinase,which provided the basis for the development and design of JAK3 inhibitors.Secologanin exhibited strong binding ability and high selectivity to JAK3 kinase through reverse screening with other JAK family members as target.This study found that secologanin may be used as highly selective inhibitors of JAK3 kinase,which was worthy of a detailed further study.

Key words: Janus kinase, inhibitor, molecular docking, TCMSP database

中图分类号:  Q74

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