Dipartimento di Scienze Farmaceutiche, Universita di Pisa, via Bonanno 6, 56126 Pisa, Italy.
J Chem Inf Model. 2009 Dec;49(12):2774-85. doi: 10.1021/ci900288e.
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 HDAC1 nearly 40 compounds that had been tested for their inhibitory activity against the two HDAC isozymes. Evaluation of the best binding poses allowed us 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.
我们开发了一种使用 Gold 软件的对接方案，用于预测组蛋白去乙酰化酶 (HDAC) 抑制剂的结合位置，从 HDAC8 的 X 射线结构开始。随后，我们使用优化后的程序将将近 40 种化合物对接进入 HDAC8 和 HDAC1 的同源模型，这些化合物已经经过测试，以评估它们对两种 HDAC 同工酶的抑制活性。对最佳结合构象的评估使我们能够确定对活性和选择性重要的配体性质和蛋白质残基。HDAC 是重要的抗癌药物靶点，目前正在积极研究。因此，我们的结果可能有助于设计新的同工酶选择性 HDAC 抑制剂。此外，这种策略也可用于其他 HDAC 的研究。
Zotero 插件