PONE-D-23-06412Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approachesPLOS ONE

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PLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The methodology and results obtained are original BUT need to be thoroughly reviewed. Overall, the manuscript is fine, however the discussion is not robust and there are a lot of grammatical issues, spelling mistakes, choice of words and poor result presentation. The authors should provide a valid response(s) to the above comment(s). The details comments are mentioned below:

1. The title should be rewrite, and revised.

2. In 2.1, all the equation should be rechecked, and should be mentioned which software has been used for optimization.

3. In 2.4, Method for Molecular Docking section, it is not clear How did author minimize the energy of the chosen receptors? Why is the removal of water and other unwanted substances necessary during protein preparation?

4. State clearly, how the active sites of the target proteins were determined and total number of active sites like hydrogen bonding, and hydrophobic bonding should be analyzed.

5. In Figure 3. Chemical structure of Scutellarein derivatives is not properly arranged, like 01,02,03,04,05,06,09, 07, 08, 09, and 10, should be rearranged, and corrected the sequences.

6. In labeling of Molecules, author sometimes used DM, sometimes use only number. It should be similar for all compounds. Please check carefully.

7. In table 6, Author have already mentioned standard drugs Capecitabine, but why should you have mentioned Fluconazole? Since it as an antifungal drug. Please check this carefully.

8. The result of molecular docking and interactions are not comprehensively discussed. Please consider revising. Also, there are some identified spelling mistakes. Please correct this appropriately

9. There are a lot of grammatical issues, spelling mistakes and choice of words in the introductory section of this manuscript. Kindly edit and correct appropriately. Use Grammarly software on other available.

I hereby recommend this paper for publication only IF the authors carefully address the comments:

Reviewer #2: The authors have chosen an area that needs attention and has tried to focus on it but there are a lot of lacunas in the study and writing of the manuscript.

1. Why was Scutellarin considered a promising candidate for this study?

2. In the abstract, describe the full name of HOMO and LUMO, since the terms were initially in the MS, after which the short form can be used.

3. What is the relevance of the pass prediction section?

4. Interaction pictures with the selected enzymes should be given. and interactions should be explained one by one.

5. In keyword sections, ‘Molecular Dynamic’ should be ‘Molecular Dynamics Simulation

6. Throughout the manuscript, certain terms are written in capital letters; please replace them with small letters.

7. Mentioned the PyRx and Discovery Studio software versions used for this study.

8. It is important for authors to identify the specific amino acid residues (hydrogen bonding, and hydrophobic bonding) formed during drug-protein complex formation.

9. Suggested updating the quality, or resolution of the images of Molecular docking pocket, hydrogen bonding, and binding interaction.

10. Determination of the Data of ADMET’ should be ‘ADMET profile prediction’

11. Finally, the Conclusion should be rewritten more briefly and covered all the information discussed in the result discussion.

12. On page no. 23 and 24, mention types of interactions with a receptor in figure legends

13. Authors only performed RMSD and RMSF, but these are not sufficient to prove the stability. It is highly recommended to calculate protein-ligand contacts over a period of simulation, radius of gyration, and solvent-accessible surface area of protein.

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Reviewer #1: Yes: Rana Adnan Tahir (Ph.D.)

Department of Biosciences,

COMSATS University Islamabad, Sahiwal Campus

Reviewer #2: Yes: Muhammad Nasir Iqbal

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A drug design strategy based on molecular docking and molecular dynamics simulations applied to development of inhibitor against triple-negative breast cancer by Scutellarein derivatives

PONE-D-23-06412R1

Dear Dr. Akash,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Sheikh Arslan Sehgal, PhD

Academic Editor

PLOS ONE

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