A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion.
A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion.
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SARS-CoV-2 病毒粒子的多尺度粗粒度模型。
DOI：
10.1101/2020.10.02.323915
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Voth,GregoryA
中科院分区：
文献类型：
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作者：
Yu,Alvin;Pak,AlexanderJ;He,Peng;Monje-Galvan,Viviana;Casalino,Lorenzo;Gaieb,Zied;Dommer,AbigailC;Amaro,RommieE;Voth,GregoryA
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）是COVID-19大流行的病原体。完整病毒颗粒的计算机模拟可以为大规模病毒过程提供理论见解，包括组装，出芽，出口，进入和融合。详细的原子模拟被限制在较短的时间尺度，并需要十亿原子模拟这些过程。在这里，我们报告了SARS-CoV-2病毒粒子的大部分“自下而上”粗粒度（CG）模型的当前状态和正在进行的开发。冷冻电子显微镜（cryo-EM），X射线晶体学和计算预测的组合数据被用来建立结构SARS-CoV-2蛋白的分子模型，然后组装成一个完整的病毒体模型。我们描述了如何CG分子相互作用可以来自全原子模拟，如何病毒的行为难以捕捉的原子模拟可以纳入CG模型，以及如何CG模型可以迭代改进的新数据变得公开。我们提出的初始CG模型和详细方法旨在为那些对SARS-CoV-2病毒体进行多尺度模拟感兴趣的COVID-19研究人员提供资源。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and ongoing development of a largely "bottom-up" coarse-grained (CG) model of the SARS-CoV-2 virion. Data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data become publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion.