Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis.
Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis.
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DOI：
10.1016/j.str.2015.05.017
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发表时间：
2015-08-04
期刊：
影响因子：
--
通讯作者：
Schulten K
中科院分区：
文献类型：
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作者：
Goh BC;Perilla JR;England MR;Heyrana KJ;Craven RC;Schulten K
定义未成熟逆转录病毒颗粒组装的六边形晶格中Gag蛋白之间的分子相互作用对于阐明病毒组装和成熟的机制至关重要。在低温电子显微镜的最新进展已经产生了亚纳米结构信息的形态不成熟的Gag晶格，使计算建模和模拟可行的调查在原子水平上的Gag-Gag相互作用。我们已经研究了劳斯肉瘤病毒（RSV）的结构，使用全原子分子动力学模拟和体外组装，以创建第一个全原子模型的未成熟逆转录病毒晶格。微秒长的复制交换分子动力学模拟的间隔肽（SP）的核衣壳（NC）的亚结构域的结果在6螺旋束具有两亲性。所得的RSV Gag晶格模型显示了衣壳蛋白（CA）的特征和动力学，对成熟过程有影响，并证实了Gag上游和下游区域（即p10和SP-NC）的稳定作用。
Defining the molecular interaction between Gag proteins in an assembled hexagonal lattice of immature retrovirus particles is crucial for elucidating the mechanisms of virus assembly and maturation. Recent advances in cryo-electron microscopy have yielded subnanometer structural information on the morphology of immature Gag lattices, making computational modeling and simulations feasible for investigating the Gag-Gag interactions at the atomic level. We have examined the structure of Rous sarcoma virus (RSV) using all-atom molecular dynamics simulations and in vitro assembly, to create the first all-atom model of an immature retroviral lattice. Microseconds-long replica exchange molecular dynamics simulation of the spacer peptide (SP)-nucleocapsid (NC) subdomains results in a 6-helix bundle with amphipathic properties. The resulting model of the RSV Gag lattice shows features and dynamics of the capsid protein (CA) with implications for the maturation process, and confirms the stabilizing role of the upstream and downstream regions of Gag, namely p10 and SP-NC.