PONE-D-24-40709Insights from Molecular Docking and Dynamics Simulations of P2RX7- Syn ComplexPLOS ONE

Dear Dr. Kumar,

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Yusuf Oloruntoyin Ayipo, Ph.D

Academic Editor

PLOS ONE

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4. Thank you for stating the following financial disclosure:

“Mukesh Kumar

No.F.7-40/Biochem./2022-23/JD(R))

ICAR-Indian Veterinary Research Institute

https://www.ivri.nic.in/

No”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

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5. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“Our present manuscript is supported by the institute funded project entitled “Elucidating the role

of alpha synuclein (SNCA) and cholesterol on regulating the P2RX7 pore dilation”

No.F.740/Biochem./2022-23/JD(R). We thank the Director, ICAR-IVRI and Joint Director

Research ICAR-IVRI for their kind support. We thank the head, Division of Biochemistry for his

valuable support and cooperation to execute the research project. We would like to thank the

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faculty of Biochemistry, Dr. Praveen Singh, Dr. Ajay Kumar and Dr. Meeta Saxena for their

valuable guidance and useful feedback. We thanked technical officer Puja and attendant Riyasat Ji

for his valuable support during conducting research in the lab. We would like to thank Dr.

Himanshu Khandelia, Asso. Professor, South Denmark University, Denmark for his valuable

suggestions during MD data analysis.”

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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“Mukesh Kumar

No.F.7-40/Biochem./2022-23/JD(R))

ICAR-Indian Veterinary Research Institute

https://www.ivri.nic.in/

No”

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Additional Editor Comments:

The submission has an ideal scientific significance, however, needs to be revised qualitatively to meet the standard for publication in this journal.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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 manuscript is solid, and the hypothesis is well-defined and supported by preliminary evidence. However, some underlying evidence obtained by the author needed to be provided in the manuscript, which negates the journal guideline. For instance, variation in the RMSD of ⍺Syn was not shown. Additionally, data on the spatiotemporal evolution of each protein was not given.

Reviewer #2: The article is a very good one which will open the way in managing neurodegenerative diseases in the future. the author was able to clearly explain the molecular interaction between P2RX7 and Syn in terms of structural pore intracellularly and extracellularly.

However, the article would be much better by having table of content. also, the method section ----- structure analysis should be change to structural analysis.

Reviewer #3: This is a good manuscript that is well written, However, the authors should endeavor to correct the little errors identified and highlighted below.

- The title is too generic, and may discourage readers, as this will be mistaken for another docking and attractive study, the problem the research addressed should be factor into the Title to make it more attractive and appealing.

- Spacing in between words and numbers such as which84, and24 spaced as “which 84”, as seen in 19

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes:  Sulyman Olalekan Ibrahim

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Attachments

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Submitted filename: PONE-D-24-40709_reviewer-FA.pdf .pdf

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Submitted filename: Reviewers Comment Plus one.docx

Mechanistic insights into Alpha-Synuclein binding to P2RX7: A molecular dynamics and docking Study

PONE-D-24-40709R1

Dear Dr. Kumar,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Yusuf Oloruntoyin Ayipo, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have responded appropriately to all my initial concerns and those of the reviewers. They have equally implemented the suggestions for improving the quality of the submission to the standard for publication in this journal. I therefore recommend its publication in the current form.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

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6. 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: (No Response)

Reviewer #3: All recommended corrections suggested to the authors have been effected, I therefore recommending acceptance of manuscript.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: Yes:  FAIZAH ALABI

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Recommendation-Plus one.docx

Attachment

Submitted filename: PONE-D-24-40709_Review (FA).pdf