计算机模拟亚甲基蓝与牙龈卟啉单胞菌部分蛋白的分子对接  

Computer simulation of molecular docking between methylene blue and some proteins of Porphyromonas gingivalis

作　　者：袁临天 马利沙 刘润园 齐伟 张栌丹 王贵燕 王宇光[2] YUAN Lin-tian;MA Li-sha;LIU Run-yuan;QI wei;ZHANG Lu-dan;WANG Gui-yan;WANG Yu-guang(Department of General Medicine, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China;Center for Digital Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China;Department of Endodontics, College of Stomatology, Dalian Medical University, Dalian 116044, Liaoning, China;First Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100081, China;Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China)

机构地区：[1]北京大学口腔医学院·口腔医院综合科,国家口腔疾病临床医学研究中心,口腔数字化医疗技术和材料国家工程实验室,口腔数字医学北京市重点实验室,北京100081 [2]北京大学口腔医学院·口腔医院口腔医学数字化研究中心,北京100081 [3]大连医科大学口腔医学院牙体牙髓科,辽宁大连116044 [4]北京大学口腔医学院·口腔医院门诊部,北京100081 [5]北京大学口腔医学院·口腔医院儿童口腔科,北京100081

出　　处：《北京大学学报（医学版）》2022年第1期23-30,共8页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(51972003);国家重点研发计划(2018YFE0192500);首都特色临床研究(Z181100001718186);北大医学交叉研究种子基金(BMU2020MX013)-中央高校基本科研业务费;北京大学医学部智慧医疗专项(BMU2019ZHYL003)。

摘　　要：目的:使用计算机模拟的靶点预测与分子对接的方法,研究抗菌光动力疗法中光敏剂与细菌结合的靶点,并计算结合能。方法:在Uniprot数据库和RCSB PDB数据库中获取并汇总牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)的蛋白名称;在SciFinder数据库、PubChem数据库、ChemSpider数据库和Chemical Book中筛选并对比亚甲基蓝的结构图,并用ChemBioDraw软件绘制确认;在PharmMapper数据库对亚甲基蓝三维结构进行靶点预测,并用Cytoscape软件构建可视化网络图;在String数据库中构建亚甲基蓝靶点与Pg蛋白交集的相互作用网络;选择FimA、Mfa4、RgpB、Kgp K1蛋白,使用AutoDock软件计算亚甲基蓝与上述蛋白的对接能量,并进行分子对接。结果:靶点预测结果显示,268个亚甲基蓝潜在靶点和1865个Pg的蛋白之间有19个共同的靶点,这19个靶点为:groS、radA、rplA、dps、fabH、pyrG、thyA、panC、RHO、frdA、ileS、bioA、def、ddl、TPR、murA、lepB、cobT、gyrB。分子对接结果显示,亚甲基蓝能与FimA蛋白的9个位点结合,结合能-6.26 kcal/mol;与Mfa4蛋白的4个位点和氢键形成位点GLU47结合,结合能-5.91 kcal/mol;与RgpB蛋白的氢键形成位点LYS80结合,结合能-5.14 kcal/mol;与Kgp K1蛋白的6个位点和氢键形成位点GLY1114结合,结合能-5.07 kcal/mol。结论:计算机模拟的靶点预测与分子对接技术可以初步揭示亚甲基蓝与Pg部分蛋白发生结合、结合程度及结合位点,为将来研究光敏剂与细胞、细菌结合位点的筛选提供参考。Objective:To study the binding target of photosensitizer and bacteria in antimicrobial photodynamic therapy with computer-simulated target prediction and molecular docking research methods and to calculate the binding energy.Methods:The protein names of Porphyromonas gingivalis(Pg)were obtained and summarized in Uniprot database and RCSB PDB database;the structure diagrams of methy-lene blue were screened in SciFinder database,PubChem database,ChemSpider database,and Chemical Book,and ChemBioDraw software was used to draw and confirm the three-dimensional structure for target prediction and Cytoscape software was used to build a visual network diagram;a protein interaction network was searched and built between the methylene blue target and the common target of Pg in the String database;then we selected FimA,Mfa4,RgpB,and Kgp K1 proteins,used AutoDock software to calculate the docking energy of methylene blue and the above-mentioned proteins and performed molecular docking.Results:The target prediction results showed that there were 19 common targets between the 268 potential targets of methylene blue and 1865 Pg proteins.The 19 targets were:groS,radA,rplA,dps,fabH,pyrG,thyA,panC,RHO,frdA,ileS,bioA,def,ddl,TPR,murA,lepB,cobT,and gyrB.The results of the molecular docking showed that methylene blue could bind to 9 sites of FimA protein,with a binding energy of-6.26 kcal/mol;with 4 sites of Mfa4 protein and hydrogen bond formation site GLU47,and the binding energy of-5.91 kcal/mol,the binding energy of LYS80,the hydrogen bond forming site of RgpB protein,was-5.14 kcal/mol,and the binding energy of 6 sites of Kgp K1 protein and the hydrogen bond forming site GLY1114 of-5.07 kcal/mol.Conclusion:Computer simulation of target prediction and molecular docking technology can initially reveal the binding,degree of binding and binding sites of methylene blue and Pg proteins.This method provides a reference for future research on the screening of binding sites of photosensitizers to cells and bacteria.

关 键 词：靶点预测 分子对接 光动力 亚甲基蓝 牙龈卟啉单胞菌 

分 类 号：R781.4[医药卫生—口腔医学]