Hsieh Yin-Chen, Poitevin Frédéric, Delarue Marc, Koehl Patrice
Department of Computer Science and Genome Center, University of California, Davis Davis, CA, USA.
Department of Structural Biology, Stanford UniversityStanford, CA, USA; SLAC National Accelerator Laboratory, Stanford PULSE InstituteMenlo Park, CA, USA.
Front Mol Biosci. 2016 Dec 27;3:85. doi: 10.3389/fmolb.2016.00085. eCollection 2016.
Key steps in the life cycle of a virus, such as the fusion event as the virus infects a host cell and its maturation process, relate to an intricate interplay between the structure and the dynamics of its constituent proteins, especially those that define its capsid, much akin to an envelope that protects its genomic material. We present a comprehensive, comparative analysis of such interplay for the capsids of two viruses from the family, Dengue (DENV) and Zika (ZIKV). We use for that purpose our own software suite, DD-NMA, which is based on normal mode analysis. We describe the elements of DD-NMA that are relevant to the analysis of large systems, such as virus capsids. In particular, we introduce our implementation of simplified elastic networks and justify their parametrization. Using DD-NMA, we illustrate the importance of packing interactions within the virus capsids on the dynamics of the E proteins of DENV and ZIKV. We identify differences between the computed atomic fluctuations of the E proteins in DENV and ZIKV and relate those differences to changes observed in their high resolution structures. We conclude with a discussion on additional analyses that are needed to fully characterize the dynamics of the two viruses.
病毒生命周期中的关键步骤，例如病毒感染宿主细胞时的融合事件及其成熟过程，都与构成病毒的蛋白质的结构和动力学之间复杂的相互作用有关，尤其是那些决定病毒衣壳的蛋白质，这很类似于保护其基因组物质的包膜。我们对黄病毒科的两种病毒——登革热病毒（DENV）和寨卡病毒（ZIKV）的衣壳进行了全面的比较分析。为此，我们使用了基于正常模式分析的自有软件套件DD-NMA。我们描述了DD-NMA中与大型系统（如病毒衣壳）分析相关的要素。特别是，我们介绍了简化弹性网络的实现方法，并说明了其参数化的依据。使用DD-NMA，我们阐述了病毒衣壳内堆积相互作用对登革热病毒和寨卡病毒E蛋白动力学的重要性。我们确定了登革热病毒和寨卡病毒E蛋白计算得到的原子涨落之间的差异，并将这些差异与它们高分辨率结构中观察到的变化联系起来。最后，我们讨论了为全面表征这两种病毒的动力学还需要进行的其他分析。
