N439K variant in spike protein may alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge which resulted in greater electrostatic complementarity. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. These findings would offer guidance on the development of neutralizing antibodies and the prevention of COVID-19.
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SciScore for 10.1101/2020.11.21.392407: (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 All structural figures were generated utilizing PyMOL software (https://pymol.org/2/). PyMOLsuggested: (PyMOL, RRID:SCR_000305)(2) Each complex was equilibrated with NVT (No. of particles, Volume, and Temperature) ensemble which temperature of the per-solvated system increased from the 0 to 310K gradually for 1ns. (3) Subsequently, a 50,000,000-step (100ns) production run was performed after 1ns NPT using GROMACS. GROMACSsuggested: (GROMACS, RRID:SCR_014565)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when …
SciScore for 10.1101/2020.11.21.392407: (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 All structural figures were generated utilizing PyMOL software (https://pymol.org/2/). PyMOLsuggested: (PyMOL, RRID:SCR_000305)(2) Each complex was equilibrated with NVT (No. of particles, Volume, and Temperature) ensemble which temperature of the per-solvated system increased from the 0 to 310K gradually for 1ns. (3) Subsequently, a 50,000,000-step (100ns) production run was performed after 1ns NPT using GROMACS. GROMACSsuggested: (GROMACS, RRID:SCR_014565)Results 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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.11.21.392407: (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 Finally, the mutated SARS-CoV-2 RBD was aligned with hACE2 and mAbs based on the RBD-hACE2 and RBD-mAbs structures using PyMOL software. PyMOLsuggested: (PyMOL, RRID:SCR_000305)For each system, MD simulations were performed using GROMACS 5.14.0, the latest CHARMM36 force field was selected, an explicit solvent model was used by an explicit TIP3P (three-point charge) model[40]. GROMACSsuggested: …SciScore for 10.1101/2020.11.21.392407: (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 Finally, the mutated SARS-CoV-2 RBD was aligned with hACE2 and mAbs based on the RBD-hACE2 and RBD-mAbs structures using PyMOL software. PyMOLsuggested: (PyMOL, RRID:SCR_000305)For each system, MD simulations were performed using GROMACS 5.14.0, the latest CHARMM36 force field was selected, an explicit solvent model was used by an explicit TIP3P (three-point charge) model[40]. GROMACSsuggested: (GROMACS, RRID:SCR_014565)Results 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.
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