Enhanced binding of the N501Y‐mutated SARS‐CoV‐2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations
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Abstract
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.
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SciScore for 10.1101/2021.01.04.425316: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources MD simulations: All-atom MD simulations were carried out for both the bound (the complex of hACE2 and sRBD) and free (stand alone sRBD) states using the NAMD2.13 package22 running on the IBM Power Cluster. NAMD2.13suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdent…
SciScore for 10.1101/2021.01.04.425316: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources MD simulations: All-atom MD simulations were carried out for both the bound (the complex of hACE2 and sRBD) and free (stand alone sRBD) states using the NAMD2.13 package22 running on the IBM Power Cluster. NAMD2.13suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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