Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS‐CoV‐2 spike protein
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Abstract
A novel coronavirus (the SARS‐CoV‐2) has been identified in January 2020 as the causal pathogen for COVID‐19, a pandemic started near the end of 2019. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS‐CoV as a receptor was found to facilitate the infection of SARS‐CoV‐2, initiated by the binding of the spike protein to human ACE2.
Methods
Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure and dynamics of the ACE2 in complex with the receptor binding domain (RBD) of the SARS‐CoV‐2 spike protein.
Results
The predicted model is highly consistent with the experimentally determined structures, validating the homology modeling results. Besides the binding interface reported in the crystal structures, novel binding poses are revealed from all‐atom MD simulations. The simulation data are used to identify critical residues at the complex interface and provide more details about the interactions between the SARS‐CoV‐2 RBD and human ACE2.
Conclusion
Simulations reveal that RBD binds to both open and closed state of ACE2. Two human ACE2 mutants and rat ACE2 are modeled to study the mutation effects on RBD binding to ACE2. The simulations show that the N‐terminal helix and the K353 are very important for the tight binding of the complex, the mutants are found to alter the binding modes of the CoV2‐RBD to ACE2.
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SciScore for 10.1101/2020.03.24.005561: (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 The simulation trajectories were propagated to 500 nanoseconds using the GROMACS 5.1.2 package19 Three independent trajectories starting from random velocities based on Maxwell distributions were simulated for both CoV2-RBD/ACE2 and SARS-RBD/ACE2 complex systems in their wild types. 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 …SciScore for 10.1101/2020.03.24.005561: (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 The simulation trajectories were propagated to 500 nanoseconds using the GROMACS 5.1.2 package19 Three independent trajectories starting from random velocities based on Maxwell distributions were simulated for both CoV2-RBD/ACE2 and SARS-RBD/ACE2 complex systems in their wild types. 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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