Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies: Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations
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SciScore for 10.1101/2021.02.21.432165: (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
Antibodies Sentences Resources We also simulated the cryo-EM structure of the SARS-CoV-2 RBD complex with the Fab fragments of two neutralizing antibodies, REGN10933 and REGN10987 (pdb id 6XDG)105 (Figure 1D-F). REGN10987suggested: None121 Mutational Sensitivity Analysis and Alanine Scanning: To compute protein stability and binding free energy changes in the SARS-CoV-2 RBD structures upon complex formation with ACE2 receptor and REGN-COV2 antibody cocktail, we conducted a systematic alanine scanning of protein residues in the SARS-CoV-2 RBD and S1 domain. Alanine Scanning: To compute protein stability and binding free energy changes …SciScore for 10.1101/2021.02.21.432165: (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
Antibodies Sentences Resources We also simulated the cryo-EM structure of the SARS-CoV-2 RBD complex with the Fab fragments of two neutralizing antibodies, REGN10933 and REGN10987 (pdb id 6XDG)105 (Figure 1D-F). REGN10987suggested: None121 Mutational Sensitivity Analysis and Alanine Scanning: To compute protein stability and binding free energy changes in the SARS-CoV-2 RBD structures upon complex formation with ACE2 receptor and REGN-COV2 antibody cocktail, we conducted a systematic alanine scanning of protein residues in the SARS-CoV-2 RBD and S1 domain. Alanine Scanning: To compute protein stability and binding free energy changes in the SARS-CoV-2 RBD structures upon complex formation with ACE2 receptor and REGN-COV2 antibody cocktail, we conducted a systematic alanine scanning of protein residues in the SARS-CoV-2 RBD and S1suggested: NoneREGN-COV2suggested: NoneIn addition, a complete mutational sensitivity analysis was done for binding free energy hotspots and residues E406, K417, N439, K444, E484, F486, and N501 targeted by widely circulating and antibody-escaping mutations. K417suggested: NoneN439suggested: NoneK444suggested: NoneE484suggested: (GenWay Biotech Inc. Cat# GWB-A8E484, RRID:AB_10274576)F486suggested: Noneantibody-escaping mutations.suggested: NoneSoftware and Algorithms Sentences Resources The CABS-flex approach implemented as a Python 2.7 object-oriented standalone package was used in this study to integrate a high-resolution coarse-grained model with robust and efficient conformational sampling proven to accurately recapitulate all-atom MD simulation trajectories of proteins on a long time scale. Pythonsuggested: (IPython, RRID:SCR_001658)The missing loops in the studied crystal structures of the dissociated S1 domain complexes with ACE2 (residues 556-573, 618-632) were reconstructed and optimized using template-based loop prediction approaches ModLoop,110 ArchPRED server111 and further confirmed by FALC (Fragment Assembly and Loop Closure) program. ArchPREDsuggested: NoneFunctional Dynamics and Collective Motions Analysis: We performed principal component analysis (PCA) of reconstructed trajectories derived from CABS-CG simulations using the CARMA package116 and also determined the essential slow mode profiles using elastic network models (ENM) analysis.117 Two elastic network models: Gaussian network model (GNM)117, 118 and Anisotropic network model (ANM) approaches119 were used to compute the amplitudes of isotropic thermal motions and directionality of anisotropic motions. CARMAsuggested: (CARMA, RRID:SCR_004999)143, 144 The network parameters were computed using the python package NetworkX139 and Cytoscape package for network analysis.145, 146 Cytoscapesuggested: (Cytoscape, RRID:SCR_003032)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 13, 82, 83, 84, 53, 22, 85, 86, 94, 27 and 30. 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.
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- No protocol registration statement was detected.
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