Coarse-Grained Modeling of Coronavirus Spike Proteins and ACE2 Receptors
Coarse-Grained Modeling of Coronavirus Spike Proteins and ACE2 Receptors
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DOI：
10.3389/fphy.2021.680983
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发表时间：
2021-06-04
影响因子：
3.1
通讯作者：
Peng, Zhangli
中科院分区：
文献类型：
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作者：
Leong, Timothy;Voleti, Chandhana;Peng, Zhangli
我们开发了SARS-CoV-2冠状病毒刺突蛋白和血管紧张素转换酶2（ACE 2）受体蛋白的粗粒度模型，以研究生理相关的时空尺度下整个冠状病毒的内吞作用。我们首先进行了全原子显式溶剂分子动力学模拟最近表征的穗和ACE 2蛋白质的结构。然后，基于蛋白质晶体结构，采用基于形状的粗粒化方法建立粗粒化模型，并从全原子模拟轨迹中提取力场参数。为了进一步分析粗粒度模型，我们对粗粒度模型进行了简正模分析，通过将内部坐标的波动与原始全原子模拟相匹配来细化力场参数。最后，我们通过模拟整个冠状病毒通过宿主细胞膜的内吞作用，证明了这些粗粒度模型的能力。我们将粗粒的尖峰模型嵌入病毒包膜表面，并将ACE 2受体锚定在宿主细胞膜上，这是使用一个颗粒厚的脂质双层模型建模的。粗粒度模拟显示，刺突蛋白在与ACE 2受体相互作用期间由于其独特的柔性而采用弯曲构型，这使得它们比刚性刺突更容易附着到宿主细胞膜上。
We developed coarse-grained models of spike proteins in SARS-CoV-2 coronavirus and angiotensin-converting enzyme 2 (ACE2) receptor proteins to study the endocytosis of a whole coronavirus under physiologically relevant spatial and temporal scales. We first conducted all-atom explicit-solvent molecular dynamics simulations of the recently characterized structures of spike and ACE2 proteins. We then established coarse-grained models using the shape-based coarse-graining approach based on the protein crystal structures and extracted the force field parameters from the all-atom simulation trajectories. To further analyze the coarse-grained models, we carried out normal mode analysis of the coarse-grained models to refine the force field parameters by matching the fluctuations of the internal coordinates with the original all-atom simulations. Finally, we demonstrated the capability of these coarse-grained models by simulating the endocytosis of a whole coronavirus through the host cell membrane. We embedded the coarse-grained models of spikes on the surface of the virus envelope and anchored ACE2 receptors on the host cell membrane, which is modeled using a one-particle-thick lipid bilayer model. The coarse-grained simulations show the spike proteins adopt bent configurations due to their unique flexibility during their interaction with the ACE2 receptors, which makes it easier for them to attach to the host cell membrane than rigid spikes.