不同pH条件下基质蛋白二聚体稳定性的分子动力学模拟  

Molecular Dynamics Simulation of Matrix Protein Dimer Stability under Different pH Conditions

作　　者：和二斌 赵炳炎 张文杰 康文斌[2] 马庆修 HE Erbin;ZHAO Bingyan;ZHANG Wenjie;KANG Wenbin;MA Qingxiu(College of Physics and Telecommunications Engineering/Guangxi Universities Key Lab of Complex System Optimization and Big Data Processing,Yulin Normal University,Yulin 537000,China;School of Public Health and Management,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]玉林师范学院物理与电信工程学院/广西高校复杂系统优化与大数据处理重点实验室,广西玉林537000 [2]湖北医药学院公共卫生与健康学院,湖北十堰442000

出　　处：《内蒙古大学学报（自然科学版）》2024年第5期509-515,共7页Journal of Inner Mongolia University：Natural Science Edition

基　　金：广西自然科学基金项目(2018GXNSFAA281185);广西高校中青年教师基础能力提升项目(2019KY0586);玉林师范学院高层次人才科研启动项目(G2017005)。

摘　　要：位于甲型流感病毒包膜下的基质蛋白M1(Matrix protein 1,M1),可以与病毒包膜上的血凝素、神经氨酸酶和病毒遗传物质发生相互作用,在病毒生命周期的许多阶段起着关键作用。在病毒进入宿主细胞和出芽的过程中,M1多聚体的稳定性受到细胞环境的严格调控。因此,揭示基质蛋白寡聚体的热力学特征及其稳定性的主要贡献因素,对于设计以基质蛋白为靶向的抗流感药物具有重要意义。本文基于流感病毒在进入宿主细胞过程中所经历的环境条件,通过标准分子动力学、拉伸模拟和伞形采样模拟,研究不同pH条件下M1二聚体的热力学性质及其稳定性。结果表明,酸性环境对M1二聚体的热力学稳定性和解离过程有显著影响,二聚体接触面上酸性残基的质子化能够降低其结合能。这些发现揭示了流感病毒在感染过程中环境因素对基质蛋白组装调控的分子机制。The matrix protein M1 located under the envelope of influenza A virus can interact with the hemagglutinin,neuraminidase,and viral genetic material on the virus envelope,playing a crucial role in many stages of the virus lifecycle.The stability of M1 polymers is strictly regulated by the cellular environment during virus entry into host cells and virus budding.Therefore,revealing the thermodynamic characteristics of matrix protein oligomers and the major contributing factors for their stability is of great significance for designing anti-influenza drugs targeting matrix proteins.In this work,based on the environmental conditions experienced by influenza virus during entry into host cells,the thermodynamic properties and stability of M1 dimers under different conditions were studied using standard molecular dynamics,tensile simulation,and umbrella sampling simulation.The results indicate that acidic environment has a significant impact on the thermodynamic stability and dissociation process of M1 dimers,and protonation of acidic residues on the dimer contact surface can reduce its binding energy.These findings reveal the molecular mechanisms by which environmental factors regulate matrix protein assembly during influenza virus infection.

关 键 词：流感病毒 基质蛋白 PH 分子动力学 

分 类 号：Q615[生物学—生物物理学] O561[理学—原子与分子物理]