Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.991 *Rheumatic fever
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2021
• Mô tả vật lý: Size: Article No. e0257905 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 259633
• Chủ đề: 1. 60 applied life sciences; 2. Ace2; 3. Biological science; 4. Molecular dynamics; 5. Receptor binding domain; 6. Sars-cov-2; 7. Spike protein

Tóm tắt

SARS-CoV-2 virus, the causative agent of Covid-19, has fired up a global pandemic. The virus interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) for an invasion via receptor binding domain (RBD) on its spike protein. To provide a deeper understanding of this interaction, we performed microsecond simulations of the RBD-ACE2 complex for SARS-CoV-2 and compared it with the closely related SARS-CoV discovered in 2003. We show residues in the RBD of SARS-CoV-2 that were mutated from SARS-CoV, collectively help make the RBD anchor much stronger to the N-terminal part of ACE2 than the corresponding residues on RBD of SARS-CoV. This would result in a reduced dissociation rate of SARS-CoV-2 from human receptor protein compared to SARS-CoV. The phenomenon was consistently observed in simulations beyond 500 ns and was reproducible across different force fields. Altogether, our study adds more insight into the critical dynamics of the key residues at the virus spike and human receptor binding interface and potentially aids the development of diagnostics and therapeutics to combat the pandemic efficiently.