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.
Molecular Dynamics Simulation of Matrix Protein Dimer Stability under Different pH Conditions
The matrix protein Ml 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 pro-teins.In this work,based on the environmental conditions experienced by influenza virus during en-try into host cells,the thermodynamic properties and stability of M1 dimers under different condi-tions were studied using standard molecular dynamics,tensile simulation,and umbrella sampling simulation.The results indicate that acidic environment has a significant impact on the thermody-namic stability and dissociation process of M1 dimers,and protonation of acidic residues on the di-mer 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.
万方数据
维普
