Dynamics and electrostatics define an allosteric druggable site within the receptor‐binding domain of SARS‐CoV‐2 spike protein
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Abstract
The pathogenesis of the SARS‐CoV‐2 virus initiates through recognition of the angiotensin‐converting enzyme 2 (ACE2) receptor of the host cells by the receptor‐binding domain (RBD) located at the spikes of the virus. Here, using molecular dynamics simulations, we have demonstrated the allosteric crosstalk within the RBD in the apo‐ and the ACE2 receptor‐bound states, revealing the contribution of the dynamics‐based correlated motions and the electrostatic energy perturbations to this crosstalk. While allostery, based on correlated motions, dominates inherent distal communication in the apo‐RBD, the electrostatic energy perturbations determine favorable pairwise crosstalk within the RBD residues upon binding to ACE2. Interestingly, the allosteric path is composed of residues which are evolutionarily conserved within closely related coronaviruses, pointing toward the biological relevance of the communication and its potential as a target for drug development.
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SciScore for 10.1101/2020.09.06.284901: (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 were performed in with both the free and bound spike protein with GROMACS 5.1.2 software16 using Amber99SB-Ildn force field17 and TIP3P water model18 with a box size of 1nm. 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 TrialI…
SciScore for 10.1101/2020.09.06.284901: (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 were performed in with both the free and bound spike protein with GROMACS 5.1.2 software16 using Amber99SB-Ildn force field17 and TIP3P water model18 with a box size of 1nm. 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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 18 and 19. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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