乙型流感病毒质子通道蛋白BM2的分子动力学模拟

发布时间：2019-06-07 16:51

【摘要】：流行性感冒(简称流感)是由流感病毒引起的急性呼吸道感染,每次大爆发在人群中有着显著的发病率和一定的致死率。乙型流感病毒引起的疾病占流感病毒的50%,会呈现周期性的大爆发,感染对象主要是老人、小孩以及孕妇等免疫力相对较低的人群。所以乙型流感病毒的研究非常重要。乙型流感病毒质子通道蛋白BM2是由四个单次跨膜蛋白单体组成的同源四聚体,BM2在病毒复制的过程中起了非常关键的作用。其跨膜段的HXXXW基序是M2蛋白形式其质子传递的选择性和门控性的关键氨基酸。阻断BM2的质子通道活性,将能在病毒感染早期有效控制病毒的复制,所以BM2有希望成为抗乙型流感病毒的药物靶点,所以对其的研究将成为对抗流感病毒研制的理论基础。分子动力学模拟是建立在牛顿力学的基础上的一种分子模拟方法,通过求解牛顿力学方程可以获得一些体系随时间变化的热力学和动力学性质。分子动力学模拟是一种对膜蛋白这种通过实验手段研究比较困难的生物体系的有效的研究方法。在生物体系中较常用的力场中,本文使用GROMACS4.5软件,选择了GROMOS87力场以及OPLS力场分别对BM2蛋白进行了25ns的分子动力学模拟。通过模拟结果的对比,可以反映两个力场在膜蛋白模拟的应用上的差异和优劣,OPLS力场更加精细的描绘了蛋白的运动情况,相对更加精细的反映水分子的分布情况。希望对分子动力学模拟的力场选择方案提出了一定的建议。OPLS力场更加精细的描绘了通道半径的变化情况,以及更加精细的反映水分子的分布情况。BM2的跨膜段PHE5和TRP23的侧链将通道堵住,这些氨基酸附近的通道半径都小于水分子半径,分别起到了N端和C端的门的作用。水分子通过PHE5、HIS19和TRP23需要越过更高的能垒。
[Abstract]:Influenza (influenza) is an acute respiratory tract infection caused by influenza virus. Each outbreak has a significant incidence and mortality in the population. The diseases caused by type B influenza virus account for 50% of the influenza virus, and there will be periodic outbreaks, mainly among the elderly, children and pregnant women with relatively low immunity. Therefore, the study of influenza B virus is very important. Type B influenza virus proton channel protein BM2 is a homologous tetramer composed of four single transmembrane protein monomers. BM2 plays a key role in the process of virus replication. The HXXXW motif of its transmembrane segment is the key amino acid of proton transfer selectivity and gating in the form of M2 protein. Blocking the proton channel activity of BM2 will effectively control the replication of the virus in the early stage of virus infection, so BM2 will hopefully become a drug target for anti-influenza B virus, so the research on it will become the theoretical basis for the development of anti-influenza virus. Molecular dynamics simulation is a kind of molecular simulation method based on Newton mechanics. The thermodynamic and dynamic properties of some systems with time can be obtained by solving Newton mechanical equations. Molecular dynamics simulation is an effective method to study membrane proteins, which is difficult to study by experimental means. In this paper, GROMOS87 force field and OPLS force field were selected to simulate the molecular dynamics of BM2 protein by using GROMACS4.5 software. Through the comparison of the simulation results, the differences and advantages and disadvantages of the two force fields in the application of membrane protein simulation can be reflected. The OPLS force field describes the movement of the protein more accurately and reflects the distribution of water molecules more precisely. It is hoped that some suggestions are put forward for the selection of force field in molecular dynamics simulation. The OPLs force field describes the variation of channel radius more precisely. The channel is blocked by the side chain of PHE5 and TRP23, and the channel radius near these amino acids is smaller than that of water molecule, which acts as the gate of N-terminal and C-terminal, respectively. the channel radius of BM2 is smaller than that of water molecule, which acts as the gate of N-terminal and C-terminal, respectively. Water molecules need to cross higher energy barriers through PHE5,HIS19 and TRP23.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R312

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