高等学校化学学报

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (11(1)): 52.

• 研究论文 • 上一篇    下一篇

羟氨酸类组蛋白去乙酰化酶抑制剂的分子对接及CoMFA研究

张亮, 相玉红, 张卓勇   

  1. 首都师范大学化学系, 北京 100048
  • 收稿日期:2009-07-28 出版日期:2009-11-30 发布日期:2009-11-30
  • 通讯作者: 张卓勇, 男, 博士, 教授, 主要从事分子光谱和化学计量学方面研究. E-mail: gusto2008@vip.sina.com
  • 基金资助:

    北京市优秀人才资助项目(批准号: 20081D0501600194)资助.

Studies on Hydroxamic Acid Histone Deacetylase Inhibitors(HDACI) by Molecular Docking and CoMFA

ZHANG Liang, XIANG Yu-Hong, Zhang Zhuo-Yong*   

  1. Department of Chemistry, Capital Normal University, Beijing 100048, China
  • Received:2009-07-28 Online:2009-11-30 Published:2009-11-30
  • Contact: Zhang Zhuo-Yong. E-mail: gusto2008@vip.sina.com
  • Supported by:

    北京市优秀人才资助项目(批准号: 20081D0501600194)资助.

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摘要：

采用Surflex-dock对接方法将组蛋白去乙酰化酶抑制剂与组蛋白酶进行对接, 通过配体与受体的相互作用揭示出此种抑制剂的结合模式. 研究结果表明, 对接自由能与抑制剂活性有较好的相关性. 利用比较分子立场分析方法(Comparative molecular field analysis, CoMFA)对此类抑制剂进行了三维定量构效关系研究,并考察了不同步长、探针原子以及电荷对构建模型的影响. 所建最佳模型交叉验证相关系数q2=0.668, 非交叉验证相关系数r2=0.984, 说明该模型预测能力较好, 可用于指导新型药物合成.

关键词: 组蛋白去乙酰化酶; Surflex-dock; 比较分子力场分析法; 抑制剂

Abstract:

Surflex-dock is used in docking histone deacetylase inhibitor and histone molecules. The interaction between ligand and receptor can revealed the binding mode of the inhibitors of HDAC. The result showed that the of docking has good correlation with the inhibitor activity. A further study on the three-dimensional quantitative structure-activity relationship(3D-QSAR) was carried out using the method of comparative mole-\{cular field analysis(CoMFA). The influences of different steps, probe atomic charge on model building were investigated. A 3D-QSAR model has been established, in which cross-validation coefficient q2 is 0.668, and non-cross-validation correlation coefficient r2 is 0.984. The established model has a good predictive ability, and it can be used to guide the drug design and synthesis.

Key words: HDAC; Surflex-dock; CoMFA; Inhibitor

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