Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane
Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane
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DOI：
10.1021/acs.jpcb.0c04553
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发表时间：
2020-08-20
影响因子：
3.3
通讯作者：
Im, Wonpil
中科院分区：
文献类型：
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作者：
Woo, Hyeonuk;Park, Sang Jun;Im, Wonpil
这项技术研究描述了病毒膜中完全糖基化的全长SARS-CoV-2刺突（S）蛋白的全原子建模和模拟。首先，从PDB开始：6VSB和6VXX，全长S蛋白结构使用基于模板的建模、从头蛋白结构预测和环建模技术在GALAXY建模套件中建模。然后，使用最近确定的最占据的糖型，使用CHARMM-GUI中的Glycan Reader & Modeler对每个单体的22个N-聚糖和1个0-聚糖进行建模。这些完全糖基化的全长S蛋白模型结构进行了评估，并使用ISOLDE在其各自的实验图谱中对低分辨率数据进行了进一步改进。然后，我们使用CHARMM-GUI Membrane Builder将S蛋白置于病毒膜中，并进行全原子分子动力学模拟。CIARMM-GUI COVID-19 Archive（http：//www.charmm-gui.org/docs/archive/covid19）中提供了所有结构，以便研究人员可以使用这些模型为COVID-19的预防和治疗进行创新和新颖的建模和模拟研究。
This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CIARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.