Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing
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SciScore for 10.1101/2020.09.09.287987: (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 We also performed composite omit map refinement implemented in PHENIX to identify potential positions of altered side chains and water molecules were checked in program COOT (Emsley & Cowtan, 2004), and positions with strong difference density were retained. PHENIXsuggested: (Phenix, RRID:SCR_014224)COOTsuggested: (Coot, RRID:SCR_014222)Temperature factor analysis and generation of ellipsoids: The two ambient-temperature Mpro in space group C121 and P212121 were examined to generate ellipsoid structures based on b-factor with PyMOL and these two structures were compared with the Mpro … SciScore for 10.1101/2020.09.09.287987: (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 We also performed composite omit map refinement implemented in PHENIX to identify potential positions of altered side chains and water molecules were checked in program COOT (Emsley & Cowtan, 2004), and positions with strong difference density were retained. PHENIXsuggested: (Phenix, RRID:SCR_014224)COOTsuggested: (Coot, RRID:SCR_014222)Temperature factor analysis and generation of ellipsoids: The two ambient-temperature Mpro in space group C121 and P212121 were examined to generate ellipsoid structures based on b-factor with PyMOL and these two structures were compared with the Mpro structures at 100 K (PDB ID: 6XKH) to provide better understanding on the flexibility of atoms, side chains and domains. PyMOLsuggested: (PyMOL, RRID:SCR_000305)All the target structures considered in this study were firstly prepared using Protein Preparation module of Maestro modeling program in which missing atoms were added, water molecules not in the vicinity of co-crystallized ligands were removed and bond orders were assigned (Madhavi Sastry et al., 2013). Maestrosuggested: (Maestro, RRID:SCR_016748)The structures of three compounds were taken from PubChem; Ebselen (PubChem ID, 3194), Tideglusib (PubChem ID: 11313622) and Carmofur (PubChem ID: 2577). PubChemsuggested: (PubChem, RRID:SCR_004284)Proceeding the production MD simulations, the systems were equilibrated using relaxation protocols of Desmond package in which a series of minimizations and short MD simulations which are performed with small time-steps at lower temperature and restrains on the nonhydrogen solute atoms in the initial stages and slowly time-steps are increased as well as simulation temperature and restrains on solute atoms are released. Desmondsuggested: (Desmond, RRID:SCR_014575)In this study, we have utilized the Bio3d package (Grant et al., 2006; Yao et al., 2013), a platform independent R package to perform PCA for considered simulation systems. Bio3dsuggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Also, knowing the beneficial and detrimental effects of targeted drugs, along with well-established precautions will help with time limitations. This procedure has emerged as a fundamental and very strategic approach not only for prospective cohort design but also for many types of clinical trials, particularly crosssectional studies because as the molecules considered in repurposing studies passed through several stages, have well-defined profiles, they would not require prolonged pre-clinical studies, and hence they are important candidates to consider in case of disease emergencies or outbreaks (Su et al., 2017; Cavalla et al., 2013; Choo et al., 2019; Aguila et al., 2020). Therefore, enormous contribution to clinical studies, repurposing is a rapid step towards the conclusion of not only randomized controlled trials but also critical structural biology investigations (Bumb et al., 2015; Pihan et al., 2012; Choudhary et al., 2020). Considering all this, adopting the drug repurposing approach and using known inhibitors ebselen, tideglusib, and carmofur to carry out Mpro-based in silico molecular docking, MD simulations and post-MD analyses make our combined study more specific. A grave issue with drug research is the variability of the target proteins as the mutations and modifications may render the found drugs ineffective (Dinesh et al., 2020). For this reason, it is only sensible to work on a protein, whose biochemical properties are conserved over time and among differe...
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 page 41. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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