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甲型流感病毒表面血凝素(HA)与神经氨酸酶(NA)之间的相互作用

发布时间:2018-09-06 15:13
【摘要】:甲型流感病毒是一种由脂质分子包覆的球状病毒,在病毒的表面分布有血凝素(hemagglutinin,简称HA蛋白)和神经氨酸酶(neuraminidase,简称NA蛋白)两种蛋白质。一般认为,在流感病毒进入宿主细胞时,HA蛋白的功能是与细胞表面的唾液酸连接,使病毒粘连在宿主表面并随着内吞作用进入宿主体内,在完成新病毒繁殖后,NA蛋白则负责将新病毒从宿主细胞释放。近年来一些实验现象表明,在病毒进入宿主的过程中,NA蛋白也会影响HA蛋白功能的发挥,但是由于方法的限制,还没有学者对这两种蛋白之间的相互作用进行深入研究。 本文使用距离矩阵和相关性系数,对HA蛋白和NA蛋白的进化过程进行了比较,发现二者具有较高的相关性,这说明HA蛋白和NA蛋白在功能上存在相互作用。随后,本文将HA蛋白和NA蛋白的序列进行划分,使用相同的方法计算各个片段之间在进化过程中的相关性,实现对两蛋白相互作用位点的搜索。最后,本文应用所找到的位点,对HA蛋白和NA蛋白发生相互作用的过程进行了分子动力学模拟,并计算了两个蛋白质在接触界面上的结合能,与实际情况下的疫情观测结果进行比较,发现两者相符,证明预测的结果是可信的。
[Abstract]:Influenza A virus is a globular virus coated with lipids. There are two proteins on the surface of influenza A virus: hemagglutinin, (HA protein) and neuraminidase (neuraminidase, protein NA protein). It is generally believed that the function of HA protein when influenza virus enters the host cell is to connect with sialic acid on the cell surface, so that the virus adheres to the host surface and enters the host body with endocytosis. The na protein is responsible for releasing the new virus from the host cells after the reproduction of the new virus. In recent years, some experimental phenomena have shown that the HA protein can also affect the function of the HA protein in the process of virus entering the host. However, due to the limitation of the methods, no further research has been done on the interaction between the two proteins. The evolutionary process of HA protein and NA protein were compared by using distance matrix and correlation coefficient. It was found that there was a high correlation between HA protein and NA protein, which indicated that there was a functional interaction between HA protein and NA protein. Then, the sequence of HA protein and NA protein were divided, and the correlation between each fragment in evolution was calculated by the same method, and the interaction sites of the two proteins were searched. Finally, the interaction between HA protein and NA protein was simulated by molecular dynamics, and the binding energy of the two proteins at the contact interface was calculated. The comparison with the observed results of epidemic situation shows that the predicted results are reliable.
【学位授予单位】:暨南大学
【学位级别】:硕士
【学位授予年份】:2011
【分类号】:R373

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