基于结构的小分子对接软件的评估与应用研究  

Evaluation and application of small molecule docking software based on structure

作　　者：曲晓虹 纪玮佳 王卓亚 陈芳玲 于日磊[2] 李伟[1] QU Xiao-hong;JI Wei-jia;WANG Zhuo-ya;CHEN Fang-ling;YU Ri-lei;LI Wei(Department of Pharmacy,Shandong Eye Hospital,Shandong Eye Institute,Shandong Academy of Medical Sciences,Qingdao 266071,China;Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Shool of Life Sciences,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]山东省医学科学院山东省眼科研究所青岛眼科医院药剂科,山东青岛266071 [2]中国海洋大学海洋药物教育部重点实验室医药学院,山东青岛266003 [3]兰州大学生命科学学院,甘肃兰州730000

出　　处：《中国海洋药物》2018年第4期23-30,共8页Chinese Journal of Marine Drugs

基　　金：国家博士后特助项目(2016T90655)资助

摘　　要：目的通过对比3种分子对接软件(MOE、LeDock、AutoDockVina)针对c-Met蛋白的虚拟筛选的准确性,选取准确性比较高的软件针对EGFR蛋白展开虚拟筛选,获得打分较高的候选化合物。方法采用虚拟筛选的方法,利用c-Met信号蛋白抑制剂作为评价体系,对MOE、AutoDockVina、LeDock 3种对接软件进行了对接结果比较,以此来评价各个软件之间的对接准确性。在此基础上,选择准确性高的软件对EGFR突变靶标开展小分子抑制剂的虚拟筛选,筛选出评价和作用良好的小分子化合物。结果与结论对比结果显示MOE和LeDock软件的对接准确度和操作简易度要高于AutoDockVina软件,并通过筛选,得到了评价良好的小分子化合物。Objective Evaluation of the accuracy of three docking packages（MOE,LeDock,and AutoDockVina）against the c-Met protein system,and selection of the software with better performance for virtual screening against the EGFR protein to obtain higher scoring candidate compounds as well as their binding modes at EGFR.Methods Virtual screening was applied to identify probable high binding affinity ligands against the EGFR proteins and determine their binding modes at EGFR.Results and Conclusion The performance of MOE and LeDock was better than AutoDockVina for virtual screening,and some small molecule compounds with high docking score were obtained by screening against the EGFR.

关 键 词：抗肿瘤 分子对接 虚拟筛选 C-MET蛋白 EGFR蛋白 

分 类 号：R917[医药卫生—药物分析学]