Molecular insights into the binding variance of the SARS-CoV-2 spike with human, cat and dog ACE2 proteins
| Autor: | Xiaohui Yuan, Xuhua Li, Zhiwei Yang, Dongxiao Hao, He Wang, Yongjian Zang, Lei Zhang, Yizhen Zhao, Shengli Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
General Physics and Astronomy
Molecular Dynamics Simulation 010402 general chemistry medicine.disease_cause 01 natural sciences 03 medical and health sciences Molecular dynamics Dogs Protein Domains medicine Animals Humans Physical and Theoretical Chemistry Receptor 030304 developmental biology chemistry.chemical_classification 0303 health sciences Mutation Principal Component Analysis SARS-CoV-2 Alanine scanning 0104 chemical sciences Amino acid Enzyme Order (biology) chemistry Spike Glycoprotein Coronavirus Biophysics Cats Thermodynamics Spike (software development) Angiotensin-Converting Enzyme 2 hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Physical chemistry chemical physics : PCCP. 23(24) |
| ISSN: | 1463-9084 |
| Popis: | SARS-CoV-2 has recently caused an epidemic in humans and poses a huge threat to global public health. As a primary receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) exists in different hosts that are in close contact with humans, especially cats and dogs. However, the underlying mechanism of how the spike receptor binding domain (RBD) of SARS-CoV-2 cooperates with human ACE2 (hACE2), cat ACE2 (cACE2) and dog ACE2 (dACE2) and the variation in binding remains largely unsolved. Therefore, we explored the binding behavior of the spike RBD with cACE2, dACE2 and hACE2 via all-atom molecular dynamics simulations. In accordance with the binding free energies and residue interactions, the spike RBD has respective binding specificities with cACE2, dACE2 and hACE2, and the binding affinities decrease in the order of hACE2, cACE2, dACE2, mainly due to changes in the amino acids Q24L, H34Y, and M82T in cACE2 or dACE2. Furthermore, alanine scanning analysis results validated some key residues of the spike RBD interact with ACE2 and provided clues to the variation of amino acid that could influence the transmissibility or immune responses of SARS-CoV-2. Decreasing dynamic correlations strengths of ACE2 with the RBD were found in all hACE2-RBD, cACE2-RBD and dACE2-RBD systems. The ACE2 protein shows variable motion modes across the zinc metallopeptidase domain, which induces different interactions between ACE2 and the RBD. Our studies reveal that the motion pattern of the zinc metallopeptidase domain is critical to the binding behavior of RBD with ACE2. These findings could aid our understanding of selective recognition involving various ACE2 with the SARS-CoV-2 spike and shed further light on the binding mechanisms. |
| Databáze: | OpenAIRE |
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