The Answer Lies in the Energy: How Simple Atomistic Molecular Dynamics Simulations May Hold the Key to Epitope Prediction on the Fully Glycosylated SARS-CoV‑2 Spike Protein
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
SARS-CoV-2 is a health threat with dire socioeconomical consequences. As the crucial mediator of infection, the viral glycosylated spike protein (S) has attracted the most attention and is at the center of efforts to develop therapeutics and diagnostics. Herein, we use an original decomposition approach to identify energetically uncoupled substructures as antibody binding sites on the fully glycosylated S. Crucially, all that is required are unbiased MD simulations; no prior knowledge of binding properties or ad hoc parameter combinations is needed. Our results are validated by experimentally confirmed structures of S in complex with anti- or nanobodies. We identify poorly coupled subdomains that are poised to host (several) epitopes and potentially involved in large functional conformational transitions. Moreover, we detect two distinct behaviors for glycans: those with stronger energetic coupling are structurally relevant and protect underlying peptidic epitopes, and those with weaker coupling could themselves be prone to antibody recognition.
Article activity feed
-
-
SciScore for 10.1101/2020.07.22.214254: (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 MINIMZATION: A 200-step minimization of each of the three protomer models is carried out using the default procedure (i.e., steepest descent for 10 steps; then conjugate gradient) implemented in the MD engine sander in the AMBER software package (version 18))46. AMBERsuggested: (AMBER, RRID:SCR_016151)MM/GBSA CALCULATIONS: MM/GBSA calculations 33 are performed on each of the three minimized ‘RBD up’ protomers using the dedicated mm_pbsa.pl utility in AmberTools (version 17). AmberToolssuggested: (AmberTools, RRID:SCR_018497)Results from OddPub: We did not detect open data. We also did not …
SciScore for 10.1101/2020.07.22.214254: (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 MINIMZATION: A 200-step minimization of each of the three protomer models is carried out using the default procedure (i.e., steepest descent for 10 steps; then conjugate gradient) implemented in the MD engine sander in the AMBER software package (version 18))46. AMBERsuggested: (AMBER, RRID:SCR_016151)MM/GBSA CALCULATIONS: MM/GBSA calculations 33 are performed on each of the three minimized ‘RBD up’ protomers using the dedicated mm_pbsa.pl utility in AmberTools (version 17). AmberToolssuggested: (AmberTools, RRID:SCR_018497)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
-
