IL-18与IL-18R分子对接计算发展模拟蛋白质相互作用研究方法  

IL-18 and IL-18R Docking Calculation to Develop the Research Approach for the Simulation of Protein Interaction

作　　者：冯悦 邱菊辉 贺佳佳 王伯初[3] 冯莹柱 Feng Yue;Qiu Juhui;He Jiajia;Wang Bochua;Feng Yingzhu(College of Pharmacy/International Institute for Innovative Targeted Medicine,Chongqing University of Arts and Sciences,Chongqing,402160;College of Chemical Engineering,Sichuan University of Science&Engineering,Zigong,643000;Key Laboratory of Biorheology Science and Technology of Ministry of Education,College of Bioengineering,Chongqing University,Chongqing,400030)

机构地区：[1]重庆文理学院药学院/创新靶向药物国际研究院,重庆402160 [2]四川轻化工大学化学工程学院,自贡643000 [3]重庆大学生物工程学院生物流变科学与技术教育部重点实验室,重庆400030

出　　处：《化学通报》2022年第12期1510-1516,1482,共8页Chemistry

基　　金：2020年度重庆市永川区新冠肺炎疫情应急科技自然科学基金项目(YCSTC,2020NB0219);2019年度重庆文理学院人才引进项目(R2019SXY12);2020年度重庆大学生物流变科学与技术教育部重点实验室开放基金课题(CQKLBST-2020-004);2020年重庆市教委研究计划项目(KJQN202001334);2021年重庆市自然科学基金青年基金项目(cstc2021jcyj-msxmX0438)资助。

摘　　要：本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R相互作用的空间结构与构象变化,计算找到了相互作用界面的氨基酸的一级序列与二级结构以及它们之间的相互作用力,并用拉氏图评估对接构象,研究发现B亚基在IL-18与IL-18R的结合中起主要作用。该计算方法与实验方法比较,可快速找到蛋白-蛋白相互作用的构象空间,优化膜蛋白相互作用的精度,其能从原子与量子水平探究细胞因子与膜蛋白受体的相互作用,其数据精确定量,有助于更深入解析分子机理。本文应用ZDOCK算法建立了通过计算模拟膜蛋白生物大分子相互作用的新领域,为细胞因子与化学因子的多肽类药物开发提供新的思路,为细菌病毒感染/肿瘤疾病的防治提供科学理论依据,在分子识别、神经元网络深度学习、生物信息处理领域具有广泛的应用。In this paper, the high-performance Discovery Studio 2021(DS2018 R2) macromolecular simulation software is applied to call the protein three-dimensional structure file in the RCSB PDB protein structure database to establish the three-dimensional(3 D) structure of the protein, and the ZDOCK program algorithm to study the spatial structure and conformation variation of the interaction between IL-18 subunit(B subunit or AB subunit) and IL-18 R. The primary sequence and secondary structure of amino acids at the interaction interface and the interaction forces between them were found by the calculation. Furthermore, the docking conformation was evaluated by Laplace diagram. It was revealed that B subunit plays a major role in the binding of IL-18 and IL-18 R. Compared with the experimental method, the computational approach can quickly find the conformational space of protein-protein interaction, optimize the accuracy of the membrane protein interaction process, and explore the interaction between cytokines and membrane protein receptors at the atomic and quantum levels, which can analyze the molecular mechanism more deeply for the data which can be accurately quantified. The research results demonstrated that the application of ZDOCK algorithm established a new field of simulation of the biological macromolecular interaction of membrane proteins by calculation, which provided a new reference for the development of polypeptide drugs of cytokines and chemokines, and a scientific theoretical basis for the prevention and treatment of bacteria/virus infection/tumor diseases. It has a wide range of applications in the fields of molecular recognition, neural network deep learning and biological information processing.

关 键 词：膜蛋白相互作用研究方法 IL-18与IL-18R分子模拟对接计算 ZDOCK 

分 类 号：Q811.4[生物学—生物工程]