Docking of Hydroxamic Acids into HDAC1 and HDAC8: A Rationalization of Activity Trends and Selectivities
Docking of Hydroxamic Acids into HDAC1 and HDAC8: A Rationalization of Activity Trends and Selectivities
复制标题
DOI：
10.1021/ci900288e
复制
发表时间：
2009-12-01
影响因子：
5.6
通讯作者：
Martinelli, Adriano
中科院分区：
文献类型：
--
作者：
Ortore, Gabriella;Di Colo, Francesco;Martinelli, Adriano
利用Gold软件开发了一种对接方案，从HDAC8的x射线结构开始预测组蛋白去乙酰化酶（HDAC）抑制剂的结合配置。随后，利用优化的程序对接到HDAC8和HDAC I的同源模型中，近40种化合物已被测试其对两种HDAC同工酶的抑制活性。对最佳结合姿势的评估使LIS能够识别配体性质和对活性和选择性重要的蛋白质残基。hdac是重要的抗癌药物靶点，其研究正在积极进行。因此，我们的结果可以帮助设计新的同工酶选择性HDAC抑制剂。此外，该策略也可用于其他hdac的研究。
A docking protocol using Gold software was developed to predict the binding disposition of histone deacetylase (HDAC) inhibitors, starting from the X-ray structures of HDAC8. The optimized procedure was subsequently utilized to dock into HDAC8 and into a homology model of HDAC I nearly 40 compounds that had been tested for their inhibitory activity against the two HDAC isozymes. Evaluation of the best binding poses allowed LIS to identify the ligand properties and the protein residues important for activity and selectivity. HDACs are important anticancer drug targets, and their Study is currently being actively pursued. As such, our results could help design new isozyme-selective HDAC inhibitors. Furthermore, this strategy may also be used for the investigation of other HDACs.