Dubey Kshatresh Dutta, Chaubey Amit Kumar, Ojha Rajendra Prasad
Department of Physics, DDU Gorakhpur University, Gorakhpur, India.
Biochim Biophys Acta. 2011 Dec;1814(12):1796-801. doi: 10.1016/j.bbapap.2011.09.012. Epub 2011 Oct 6.
The entry of dengue viruses is mediated by pH triggering in the host cells. Here we have studied the DENV E protein stability and binding of its units at low and normal pH using MD and MM-PB/SA method for the first time. To investigate the role of pH in dissociation of dimeric protein, we have performed a concise study of hydrogen bonding and other interactions between units of dimer at low and normal pH. The Generalized Born calculation connotes that dimeric unit was relatively less stable and less proned for dimerisation at low pH. Our results provide a theoretical verification for previous assumptions of pH triggering mechanism of dengue envelope protein. During the pH alteration, we found a large decrement in salt bridges which were observed at normal pH. We also compared the flexibility of each unit and found that they exhibit different fluctuations during molecular dynamics simulations.
登革病毒的进入是由宿主细胞中的pH触发介导的。在此，我们首次使用分子动力学（MD）和MM-PB/SA方法研究了登革病毒E蛋白在低pH和正常pH下的稳定性及其亚基的结合情况。为了研究pH在二聚体蛋白解离中的作用，我们对低pH和正常pH下二聚体亚基之间的氢键及其他相互作用进行了简要研究。广义玻恩计算表明，二聚体亚基在低pH下相对不稳定，且形成二聚体的倾向较小。我们的结果为先前关于登革病毒包膜蛋白pH触发机制的假设提供了理论验证。在pH改变过程中，我们发现正常pH下观察到的盐桥数量大幅减少。我们还比较了每个亚基的柔韧性，发现它们在分子动力学模拟中表现出不同的波动。
