讲座题目：Time-dependent HDAC2 Selective Inhibitor Design

Abstract:

Development of the selective Histone Deacetylase (HDAC) inhibitors remains a significant challenge due to highly structural similarity among the 11 zinc-dependent HDAC isoforms. Among the HDAC isoforms, it is particularly difficult to achieve isoform inhibition selectivity between HDAC1 and HDAC2, since they share a very high sequence similarity (97.8%), have the same conserved residues around the catalytic pocket, and the RMSD of two aligned protein crystal structures is only 0.7 Å. As a result, it has been very challenging to develop an HDAC2 selective inhibitor by employing conventional structure-based or ligand-based drug design approaches. Herein, I will share a story on how to use the Quantum Mechanics/Molecular Mechanics (QM/MM) calculation and experimental validation to design a time-dependent HDAC2-selective inhibitor, β-hydroxymethyl chalcone, by taking advantage of the enzymatic reactivity difference.

个人简介：

巫瑞波教授，博导。广东省杰出青年基金、广东省科技创新青年拔尖人才和广州市珠江科技新星获得者。主持了国家自然科学基金面上项目和青年基金等7个科研项目。在JACS、ACIE、ACS Chem Biol、ACS Catal等杂志发表SCI论文30余篇(其中通讯作者论文19篇)。

研究方向:

专注于量子药物化学(Quantum Medicinal Chemistry)。主要涉足三方面：

(1) 针对表观遗传修饰领域靶标，开展基于反应机制的选择性抑制剂设计。

(2) 萜类天然产物生源机制研究、蛋白设计和计算辅助天然产物结构鉴定。

(3) 发展QM/MM药物设计新策略，开发新型靶向打分函数和锌蛋白力场。

更多信息请查看网页：http://sps.sysu.edu.cn/User/216.aspx

讲座地点：药学院426

讲座时间：6月1日上午10点