基于蛋白质结构的天然产物活性筛选研究进展

Progress in Structure-based Screening of Active Natural Products

近年来从中药和天然药物中发现新药已成为药物研究领域的热点。虽然从中药和天然药物中能够分离得到大量新化合物,但通常这些新化合物的作用靶点难于确定,而且由于其收率较低,限制了进一步的药理学机制研究。因此,应用基于蛋白质结构的虚拟筛选方法,结合蛋白质生物化学和药理学加以验证,能够大大缩短研究时间并降低对化合物产量的需求。综述基于蛋白质结构-分子对接的天然产物活性筛选方法、虚拟筛选常用软件、天然产物数据库、结构生物学基本方法、蛋白质结构数据库(PDB)、筛选结果的实验性验证方法,以及虚拟筛选方法发现天然产物为先导化合物的成功应用实例,以期为天然药物活性成分的快速发现提供参考。

The discovery of new drugs from traditional Chinese materia medica and natural products has become the focus in the field of drug research. Although a lot of new compounds could be obtained, it is difficult to identify their targets and conduct investigations on their pharmacological mechanisms due to limited yields. Therefore, structure-based virtual screening, combined with experimental verification of protein biochemistry and pharmacology, could greatly reduce time cost and compound consumption. This review summarized the screening method of natural products by molecular docking, commonly used softwares for virtual screening, databases of natural products, methods of structural biology, protein data bank（PDB）, methods of experimental verification, and some successful examples of lead compound obtained from natural products by virtual screening, so as to provide reference for the rapid discovery of active ingredients from natural products.