Multiscale Computer Simulation of the Immature HIV-1 Virion
Multiscale Computer Simulation of the Immature HIV-1 Virion
复制标题
未成熟 HIV-1 病毒体的多尺度计算机模拟
DOI：
10.1016/j.bpj.2010.08.018
复制
发表时间：
2010-11-03
影响因子：
3.4
通讯作者：
Voth, Gregory A.
中科院分区：
文献类型：
--
作者：
Ayton, Gary S.;Voth, Gregory A.
多尺度计算机模拟，采用实验数据和粗粒化方法相结合，用于探索未成熟的HIV-1病毒粒子的结构。一个粗粒度（CG）表示的病毒粒子膜壳和Gag多肽分子水平的信息。从电子cryotomography实验的结果的基础上，在一定条件下的模拟揭示了存在一个不完整的p6六聚体晶格形成的六聚束的加格CA域。特别是，在CG水平的未成熟的Gag晶格的形成和稳定性需要增强的CA蛋白C-末端结构域（CTD）的界面相互作用。CG表示回到分子水平的精确映射，然后允许详细的原子分子动力学研究，以确认这些增强CA（CTD）相互作用的存在，并探测其可能的起源。多尺度模拟进一步提供了对可能破坏或修改未成熟HIV-1病毒体中Gag未成熟晶格组装过程的潜在CA（CTD）突变的深入了解。
Multiscale computer simulations, employing a combination of experimental data and coarse-graining methods, are used to explore the structure of the immature HIV-1 virion. A coarse-grained (CG) representation is developed for the virion membrane shell and Gag polypeptides using molecular level information. Building on the results from electron cryotomography experiments, the simulations under certain conditions reveal the existence of an incomplete p6 hexameric lattice formed from hexameric bundles of the Gag CA domains. In particular, the formation and stability of the immature Gag lattice at the CG level requires enhanced interfacial interactions of the CA protein C-terminal domains (CTDs). An exact mapping of the CG representation back to the molecular level then allows for detailed atomistic molecular dynamics studies to confirm the existence of these enhanced CA(CTD) interactions and to probe their possible origin. The multiscale simulations further provide insight into potential CA(CTD) mutations that may disrupt or modify the Gag immature lattice assembly process in the immature HIV-1 virion.