以c-MET为抗癌靶点的海洋小分子虚拟筛选  

Virtual screening of Marine small molecules with c-MET as an anticancer target

作　　者：罗连响 郑晓祺 王渠 罗辉 LUO Lian-xiang;ZHENG Xiao-qi;WANG Qu;LUO Hui(Southern Marine Science and Engineering Guangdong Laboratory(Zhanjiang),Zhanjiang 524023,China;The Marine Biomedical Research Institute,Guangdong Medical University,Zhanjiang 524023,China;Marine Medical Research Institute of Zhanjiang,Zhanjiang 524023,China;The First Clinical College,Guangdong Medical University,Zhanjiang 524023,China)

机构地区：[1]南方海洋科学与工程广东省实验室(湛江),广东湛江524023 [2]广东医科大学海洋医药研究院,广东湛江524023 [3]广东湛江海洋医药研究院,广东湛江524023 [4]广东医科大学第一临床医学院,广东湛江524023

出　　处：《中国海洋药物》2022年第3期57-63,共7页Chinese Journal of Marine Drugs

基　　金：南方海洋科学与工程广东省实验室(湛江)(湛江湾实验室)项目(ZJW-2019-07);湛江市科技计划项目(2019A01009);广东省基础与应用基础研究基金项目(2019A1515110201);广东医科大学学科建设项目(4sG21004G)资助。

摘　　要：目的 运用计算机虚拟筛选技术和分子动力学模拟寻找海洋小分子库中抗癌靶点c-MET的小分子抑制剂。方法 利用schrodinger中Ligand Docking模块对海藻代谢物数据库(s WMD)和PDB网站检索的c-MET蛋白(PDB:2RFs)进行基于受体的分子对接筛选,采用对接得分前十的结果,利用swiss ADME网站进行成药性分析(ADME)。最后将最好的结果用Gromacs进行分子动力学模拟。结果 分子对接结果显示打分前十的化合物都能与蛋白有较好的结合效果和对接姿势,蛋白与化合物之间的相互作用主要以氢键作用为主。分子动力学结果显示配体能在受体的结合口袋中稳定存在,同时具备较为稳定的对接构象。结论 基于分子对接技术和分子动力学虚拟筛选潜在的抗癌靶点c-MET的小分子抑制剂,为研发抗癌海洋药物提供科学指导与理论依据。Objective To search for small molecule inhibitors of cancer target c-MET in Marine small Molecular Library by using computer virtual screening technology and molecular dynamics simulation. Methods The Ligand Docking module in schrodinger was used to investigate the C-MET protein retrieved from the seaweed Metabolite Database(sWMD) and PDB website.2RFs was used for molecular docking screening based on receptor, and the results of the top ten docking scores were used for drug resistance analysis using swiss ADME website. Finally, the best results were simulated with Gromacs. Results The molecular docking results showed that the top 10 compounds had good binding effect and docking position with proteins, and the interaction between proteins and compounds was mainly hydrogen bonding. Molecular dynamics results showed that the ligand existed stably in the binding pocket of the receptor and had a relatively stable docking conformation.Conclusion Based on molecular docking technology and molecular dynamics virtual screening of small molecule inhibitors of potential anticancer target c-MET, it provided scientific guidance and theoretical basis for the research and development of anticancer marine drugs.

关 键 词：C-MET 分子对接 分子动力学 海洋小分子 ADME筛选 

分 类 号：R931.77[医药卫生—生药学]