Enhanced binding of the N501Y‐mutated SARS‐CoV‐2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations
| Autor: | Binquan Luan, Tien Huynh, Haoran Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Mutation Missense Biophysics ACE2 Plasma protein binding Molecular Dynamics Simulation Bioenergetics spike protein medicine.disease_cause Biochemistry SARS‐CoV‐2 03 medical and health sciences Molecular dynamics Structural Biology antibody Research Letter Genetics medicine Humans N501Y Receptor Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Mutation biology SARS-CoV-2 Chemistry 030302 biochemistry & molecular biology Spike Protein Cell Biology Cell biology Enzyme Amino Acid Substitution Spike Glycoprotein Coronavirus biology.protein Angiotensin-Converting Enzyme 2 Antibody Hydrophobic and Hydrophilic Interactions Protein Binding |
| Zdroj: | Febs Letters |
| ISSN: | 1873-3468 0014-5793 |
| Popis: | Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (B.1.1.7 and B.1351) have emerged harbouring mutations that make them highly contagious. The N501Y mutation within the receptor-binding domain (RBD) of the spike protein of these SARS-CoV-2 variants may enhance binding to the human angiotensin-converting enzyme 2 (hACE2). However, no molecular explanation for such an enhanced affinity has so far been provided. Here, using all-atom molecular dynamics simulations, we show that Y501 in the mutated RBD can be well-coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, which may increase the overall binding affinity of the RBD for hACE2 by approximately 0.81 kcal·mol-1 . The binding dynamics revealed in our study may provide a working model to facilitate the design of more effective antibodies. |
| Databáze: | OpenAIRE |
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