The Electrostatic Features of Dengue Virus Capsid Assembly
The Electrostatic Features of Dengue Virus Capsid Assembly
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DOI：
10.1142/s2737416520420089
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发表时间：
2021-03-01
影响因子：
2.2
通讯作者：
Li, Lin
中科院分区：
文献类型：
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作者：
Lopez-Hernandez, Alan E.;Xie, Yixin;Li, Lin
登革热病毒在世界上引起严重的疾病和死亡。了解登革病毒的基本机制是开发登革病毒引起的疾病的治疗方法的高度要求。在这里，我们提出了一个计算工作，重点是登革热病毒衣壳的稳定性。利用几种计算方法研究了登革病毒衣壳上E蛋白之间的相互作用。结果发现，单个E蛋白单体上的静电分布是高度不均匀的，这使得一个E蛋白与另一个E蛋白强烈结合。这就是为什么所有的E蛋白形成同源二聚体作为整个登革病毒衣壳上的基本单位的原因。E蛋白的pKa计算表明，E蛋白的折叠能在pH 6-10范围内较低且稳定，这与许多在一定pH下稳定的蛋白质不同。E蛋白同二聚体结合能的pH依赖性表明，当pH也在6-10范围内时，结合能较低且与pH无关。这一发现表明登革病毒可以在很宽的pH范围内存活，这可以解释登革病毒在世界范围内分布如此广泛且传播速度如此之快的原因。了解登革病毒的基本机制对于开发登革病毒引起的疾病的治疗方法是非常必要的。在这里，我们提出了一个计算工作，重点是登革热病毒衣壳的稳定性。这项工作发现，登革热病毒的E蛋白可以在很宽的pH范围内存活，这可以解释为什么登革热病毒在世界范围内分布如此广泛，传播速度如此之快。
Dengue virus causes serious diseases and deaths in the world. Understanding the fundamental mechanisms of dengue virus is highly demanded to develop treatments for dengue virus caused diseases. Here, we present a computational work which focused on the stability of dengue viral capsid. The interactions among E proteins on the dengue viral capsid were studied using several computational approaches. It was found that the electrostatic distribution on a single E protein monomer is highly inhomogeneous, which makes an E protein strongly binding with another E protein. This is the reason why all the E proteins form homodimers as the basic units on the whole dengue viral capsids. The pKa calculations of E proteins demonstrated that the folding energy of an E protein is low and stable in the range of pH 6-10, which is different from many other proteins that are stable at certain pH. The pH dependence of binding energy of E protein homodimer shows that the binding energy is low and independent from pH when the pH is also in the range of 6-10. This finding implies that the dengue virus can survive in a wide range of pH, which can explain why the dengue virus is so widely distributed in the world and spreads fast.Understanding the fundamental mechanisms of dengue virus is highly demanded to develop treatments for dengue virus caused diseases. Here we present a computational work which focused on the stability of dengue viral capsid. This work found that the E proteins of dengue virus can survive in a wide range of pH, which can explain why the dengue virus is so widely distributed in the world and spreads fast.