Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure

  1. Stephen A. Wells

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Abstract

The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19.

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    SciScore for 10.1101/2020.03.10.986190: (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
    SentencesResources
    Visualisations: visualisation and some minor structural editing, viz. generation of symmetry copies, removal of water and other heterogroups, removal of alternate sidechain conformations, and renumbering of entries after addition of hydrogens, were carried out with the PyMOL viewer, version 0.99[12].
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Process structure through the MolProbity website, adding hydrogens at electron-cloud positions, accepting all recommendations for side chain flips.
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)

    Results from OddPub: Thank you for sharing your data.

    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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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.

    About SciScore

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  2. Version published to 10.1101/2020.03.10.986190v1 on bioRxiv