Title; Molecular interaction of a putative inhibitor with bacterial SHV protein.
Comments;In my view, the results obtained in this study are worthy for publication. The manuscript needs major essential revision before publication. I would like to overview the revised version of the manuscript. I have the following comments/suggestions for authors to address before final decision on the manuscript.
1. Abstract contains many inconclusive data and is very poorly written in a non-scientific way.
For example:
a. Publication quality images (importantly, the graph for RMSD versus simulation time) were generated.
b. This simulation was implemented for ~71 hr. And many more.
2. Introduction section lacks architectural data on enzymes and also misses the rationale and objectives of the study.
3.SHV should be defined in the title of the manuscript.
4. The Abstract is very poorly written. The authors have included information that is not relevant to this section. For example: “This simulation was implemented for ~71 hr. The program used a specific language named YANACONDA for performing complex tasks. Publication quality images (importantly, the graph for RMSD versus simulation time) were generated. Snapshots were retrieved after each 250 ps interval.”; “The macro command ‘md_analyze.mcr’ extracted 405 snapshots.”
5. Why 101 ns MD simulations were performed?
6. Provide citations for the PDB ID mentioned in the manuscript. Also, what were the criteria for the selection of PDB ID?
7. The “‘stick’ (red) and CPK (green)” representation of ligand and reference molecule is not clear in the figure. Authors should re-draw the figure by assigning similar models for both ligands.
8. Include the limitations of the study in the last paragraph of the Discussions section.
9. In the Introduction section the author should refer to the research paper and comment on recent in-silico techniques. It will be good information for the readers. I would like to recommend several papers, among many others, providing further explanation on this topic: PMID: 32619131 PMID: 21989830 PMID: 35315127 PMID: 34299222 PMID: 23383724
10. Incorrect sentence “The current need of a robust anti-SHV ligand is palpable”.
11. In the entire manuscript authors have used many non-scientific words which makes the study rewritten by native English speakers.
12. Justify the rationale behind the statement for cut-off value “Candidate inhibitors that demonstrated a ‘VINA-docking score’ > -7.0 were disqualified”
13. Methodology section misses VINA parameters required for docking analysis.
14. What does it means “Binding Crevice” Authors have used inappropriate words throughout the manuscript the whole manuscript needs to be validated by providing stronger justifications with relevant references.
15. The manuscript is full of grammatical errors, punctuation mistakes, and incomplete sentences.
16. Authors should avoid mentioning the software used for study in the abstract section. Just mention the important results of the study. I thought the authors should rephrase it.
17. “The entry having the accession code 4ZAM in the protein data bank was selected as the reference complex for the present work.” Citation is missing for the PDB id.
18. “Candidate inhibitors that demonstrated a ‘VINA-docking score’ > -7.0 were disqualified.” Authors should mention the units for docking score. Also made corrections throughout the MS.
19. In Figure 3 there is one unfavorable acceptor-acceptor interaction made by Ser70. So how is it important for the protein-ligand complex?
20. “Several plots like the plot displaying the radius of gyration of the solute along the progress of simulation and the one depicting ligand conformation RMSD versus simulation time were not included herein for brevity.” In my opinion it should be provided in supplementary information.
21. Results and discussion are written very poorly except for RMSD analysis. Merely putting the images and not explaining them in text does not make any sense.
22. Authors have done MD dynamic simulations for only top hit molecules. In my opinion, standards should be used for comparison studies.
23. “Figure 11: Visualization of the dynamic cross-correlation matrix” It is not upto the mark to provide proper image showing values for X,Y axis.