Laboratoire de Physique des Solides, CNRS, Univ. Paris-Sud, Université Paris-Saclay , 91405 Orsay Cedex, France.
GREMAN, UMR 7347, CNRS, Université de Tours , 37200 Tours , France.
J Phys Chem B. 2018 Oct 18;122(41):9490-9498. doi: 10.1021/acs.jpcb.8b08026. Epub 2018 Oct 5.
The formation of a viral particle generally involves hundreds of proteins, making the assembly process intricate. Despite its intrinsic complexity, the production of a viral particle begins through the interaction between the basic assembly components. For the cowpea chlorotic mottle virus (CCMV), the first steps of the assembly process involve dimers of the capsid protein. Here, we carried out atomistic molecular dynamics simulations to investigate the initial assembly process of CCMV to get insight into the interactions at the molecular level. We found that salinity not only affects the electrostatic interactions between dimers but also changes the conformation of the positively charged N-terminal tails and can cause a serious steric hindrance for other dimers binding to the hydrophobic domains. An RNA rod was used to mimic a long segment of a viral genome and to study its interaction with dimers. We observed that the dimer with tails prefers to bind on the RNA rod with its positively charged inner side. The dimer-RNA interaction was found to be as strong as the dimer-dimer interaction, whereas the association energies between a dimer and a pentamer or a hexamer of dimers were high but strongly depended on the presence of the tails. Upon heating, the capsid experienced a shrinkage accompanied by a loss of order in the icosahedral crystal structure.
病毒粒子的形成通常涉及数百种蛋白质，使得组装过程非常复杂。尽管其内在结构复杂，但病毒粒子的产生始于基本组装成分之间的相互作用。对于豇豆花叶病毒（CCMV），组装过程的第一步涉及衣壳蛋白的二聚体。在这里，我们进行了原子分子动力学模拟，以研究 CCMV 的初始组装过程，从而深入了解分子水平上的相互作用。我们发现，盐度不仅影响二聚体之间的静电相互作用，还改变了带正电荷的 N 端尾部的构象，并可能导致其他二聚体与疏水区结合时产生严重的空间位阻。我们使用 RNA 棒模拟病毒基因组的长片段，并研究其与二聚体的相互作用。我们观察到带有尾部的二聚体更喜欢与带正电荷的内侧结合在 RNA 棒上。发现二聚体-RNA 相互作用与二聚体-二聚体相互作用一样强，而二聚体与五聚体或六聚体的二聚体之间的结合能虽然很高，但强烈依赖于尾部的存在。加热后，衣壳经历了收缩，同时二十面体晶体结构的有序性丧失。
