化学学报 ›› 2011, Vol. 69 ›› Issue (12): 1399-1402. 上一篇    下一篇

研究论文

极光激酶A抗癌抑制剂的高通量筛选及对接研究

杨锐1,韩葳葳*,2,王嵩*,3   

  1. (1北华大学化学与生物学院 吉林 132013)
    (2吉林大学分子酶学工程教育部重点实验室 长春 130023)
    (3吉林大学理论化学研究所理论化学计算国家重点实验室 长春 130061)
  • 收稿日期:2010-06-07 修回日期:2010-11-10 出版日期:2011-06-28 发布日期:2011-02-27
  • 通讯作者: 王嵩 E-mail:song36@gmail.com

High-throughout Screening with Computer of a Inhibitor of Aurora A and Docking Study

Yang Rui1 Han Weiwei*,2 Wang Song*,3   

  1. (1 Department of Chemistry and Biology, Beihua University, Jilin 132013)
    (2 Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023)
    (3 State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130061)
  • Received:2010-06-07 Revised:2010-11-10 Online:2011-06-28 Published:2011-02-27

极光激酶(aurora kinases)A是负责调控细胞有丝分裂的一类重要的丝氨酸/苏氨酸激酶. 用极光激酶A的一种抑制剂H-89作为先导化合物, 通过AutoDock vina软件进行虚拟筛选, 选取能量打分最低的抑制剂(命名为H-89-1)做进一步的深入研究. 理论对接研究揭示H-89-1是一种比H-89更好的抑制剂, 并且Thr217和Arg137是H-89-1和酶作用中的重要残基, 因为它们和H-89-1形成了氢键. 我们的研究将为极光激酶A专有抑制剂的设计提供可靠的理论线索.

关键词: 极光激酶A, 分子对接, H-89, 抑制剂

Aurora A is a key member of a closely related subgroup of serine/threonine kinase that plays an important role in the completion of essential mitotic events. In order to design a potent inhibitor for aurora A, H-89 is selected as lead compound and AutoDock vina is used to dock. In the end, the new compound with the lowest binding energy with aurora A is selected to further investigation. The docking results show that the new compound (named H-89-1) is a better inhibitor than that of H-89 and Thr217 and Arg137 are important in inhibition as they form hydrogen bonds and have strong nonbonding interaction with the new inhibitor. Our results will be helpful for further experimental investigations.

Key words: Aurora A, docking, H-89, inhibitor