基于分子模拟技术筛选具有潜在治疗非小细胞肺癌的ROS1激酶抑制化合物  

Screening of ROS1 kinase inhibitor compounds with potential for the treatment of NSCLC based on molecular simulation technology

作　　者：刘飞远 梁佳龙 孙智勇[1] 陈伟[1] 刘建青[3] Liu Feiyuan;Liang Jialong;Sun Zhiyong;Chen Wei;Liu Jianqing;无(The 946th Hospital of the People’s Liberation Army(PLA),Yining 835000,Xinjiang,China;School of Pharmacy,Air Force Medical University,Xi’an,710032,Shanxi,China;School of Biological Science and Technology,Baotou Teachers College,Baotou 014030,Inner Mongolia,China)

机构地区：[1]中国人民解放军陆军第946医院,新疆伊宁835000 [2]空军军医大学药学院,陕西西安710032 [3]包头师范学院生物科学与技术学院,内蒙古包头014030

出　　处：《贵州医药》2024年第1期17-20,共4页Guizhou Medical Journal

基　　金：全军后勤科研计划面上项目(CLJ20J027);国家自然科学基金地区项目(81760590);内蒙古自然科学基金项目(2020MS03072)。

摘　　要：目的基于分子模拟技术筛选具有潜在治疗非小细胞肺癌的ROS1激酶抑制化合物。方法本研究构建了肉瘤致癌因子ROS1受体及其抑制剂之间的药效团模型,通过化合物数据库筛选、分子对接、分子动力学模拟等方法,找到一种具有抑制ROS1功能的先导化合物,最后对该抑制剂的先导化合物与受体蛋白结合作用的模式进行了分析。结果筛选得到的75号化合物在与ROS1蛋白的分子动力学模拟过程中,显示出了比较稳定的相互作用。结论75号化合物可以作为潜在的抑制ROS1的先导化合物。Objective To screen ROS1 kinase inhibitor compounds with potential for the treatment of non-small cell lung cancer based on molecular simulation technology.Methods In this study,a pharmacophore model between the sarcoma oncogenic factor ROS1 receptor and its inhibitors was constructed.Through compound database screening,molecular docking,molecular dynamics simulation and other methods,a lead compound with the function of inhibiting ROS1 was found.Finally,the mode of binding between the lead compound of the inhibitor and the receptor protein was analyzed.Results The compound No.75 obtained by screening showed a relatively stable interaction with the ROS1 protein during the molecular dynamics simulation.Conclusion Compound 75 can be used as a potential lead compound to inhibit ROS1.

关 键 词：分子模拟 ROS1抑制剂 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]