基于分子对接方法的木犀草素和罗汉松脂素与p38α激酶的分子作用机制研究  

Study on Molecular Interaction Mechanism of Luteolinand Matairesino with p38αKinase Based on Molecular Docking Method

作　　者：张铭 赵海珍 张莉 苏彦雷 冉挺 魏计超[5] 段绪红 Zhang Ming;Zhao Haizhen;Zhang Li;Su Yanlei;Ran Ting;Wei Jichao;Duan Xuhong(Pharmaceutical Equipment Divi-sion,Shijiazhuang Ping’an Hospital,Shijiazhuang 050000,China;Department of Oncology,Shijiazhuang Ping’an Hospital;De-partment of Pharmacy,the 980th Hospital of the Logistics Support Force of the PLA;School of Pharmaceutical Sciences,Xiamen U-niversity;Department of Pharmacy,Third Hospital of Hebei Medical University;College of Pharmacy,Hebei University of Chi-nese Medicine)

机构地区：[1]石家庄平安医院药械科,石家庄050000 [2]石家庄平安医院肿瘤科 [3]中国人民解放军联勤保障部队第九八〇医院药剂科 [4]厦门大学药学院 [5]河北医科大学第三医院药剂科 [6]河北中医学院药学院

出　　处：《中国药师》2021年第10期1847-1852,共6页China Pharmacist

基　　金：河北省中医药管理局科研计划基金项目(编号:2020180);河北省中医药管理局科研计划基金项目(编号:2014070);国家中医药管理局全国中药特色技术传承人才培训项目(编号:T20194828003);中国人民解放军联勤保障部队第九八〇医院科研基金项目(编号:201429)。

摘　　要：目的:研究络石藤中化合物木犀草素和罗汉松脂素与p38α之间的分子相互作用机制。方法:以p38α激酶抑制剂SB-203580、BIRB-796为阳性对照化合物,利用分子对接技术研究木犀草素和罗汉松脂素与p38α激酶在三维空间上的相互作用。结果:所有化合物均以非共价键方式与靶酶活性位点结合,形成生氢键、疏水等相互作用。SB-203580与p38α激酶的对接结合能为-9.0 kcal·mol^(-1),BIRB-796的对接能量为-11.0 kcal·mol^(-1),木犀草素对接能量-8.8 kcal·mol^(-1),罗汉松脂素对接能量为-8.2 kcal·mol^(-1),木犀草素、罗汉松脂素与p38α激酶活性位点处的结合强度与SB-203580相近,两者可竞争性阻碍该靶酶活性位点与腺嘌呤核苷三磷酸(ATP)的结合从而抑制该靶酶上调炎症因子水平的生物学活性。结论:木犀草素和罗汉松脂素应该是络石藤中抗风湿作用的活性代表成分,从分子间相互作用层面证实两者可抑制p38α激酶生物学活性从而起到抗炎作用,也给新型p38α激酶抑制剂的研发提供参考。Objective:To investigate the molecular interaction mechanism between compounds luteolin and matairesino in trachelospermum jasminoides and p38α.Methods:SB-203580 and BIRB-796,the classical inhibitors of p38αkinase,were used as the positive control compounds,and molecular docking software Autodock Vina was used to study the interaction of luteolin and matairesino with p38αkinase in three-dimensional space.Results:All compounds bound to the active sites of target enzyme by non-covalent bond,forming hydrogen bond,hydrophobic effect and other interactions.The docking free energy to p38αkinase was-9.0 kcal·mol^(-1) for SB-203580,-11.0 kcal·mol^(-1) for BIRB-796,-8.8 kcal·mol^(-1) for luteolin and-8.2 kcal·mol^(-1) for matairesino.The binding strength of luteolin and matairesino to the active site of p38αkinase was similar to that of SB-203580,both of which competitively blocked the binding between the active site of target enzyme and ATP,thus inhibiting the biological activity of target enzyme to up-regulate the inflammatory factors.Conclusion:Luteolin and matairesino should be the active representative ingredients of trachelospermum jasminoides against rheumatism.This study has confirmed that they can inhibit the biological activity of p38αkinase and play an anti-inflammatory role from the level of intermolecular interaction,which provides reference for the research and development of new p38αkinase inhibitors.

关 键 词：络石藤 木犀草素 罗汉松脂素 P38丝裂原活化蛋白激酶 分子对接 抗风湿 

分 类 号：R966[医药卫生—药理学]