The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 576.8 Evolution
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021
• Mô tả vật lý: : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261726
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. 97 mathematics and computing; 4. Biomolecular modeling; 5. Coronavirus; 6. Covid19; 7. Immunogen design; 8. Molecular dynamics simulations; 9. Sars-cov-2

Tóm tắt

The COVID-19 pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the ?D-form? to the ?G-form?) that carried an amino acid substitution D614G in its ?Spike? protein. The G-form is more infectious in vitro and associated with increased viral loads. To gain insight into the molecular-level underpinnings of these characteristics, we employed microsecond all-atom simulations. Here we show that changes in the protein energetics favor a higher population of infection-capable (open) states through release of hydrogen bonds of an asymmetry present in the D-form but not the G-form. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are significant for vaccine design. The Molecular Dynamics Simulations datasets generated in this study, namely that of the soluble form SARS-CoV-2 Spike protein are made available here. Details of the trajectory and supporting files are given in the README.txt file.