PONE-D-23-18239Divide, conquer and reconstruct: how to solve the 3D structure of recalcitrant Micro-Exon Gene (MEG) protein from Schistosoma mansoniPLOS ONE

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Comments to the Author

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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

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

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: 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 “Divide, conquer and reconstruct: how to solve the 3D structure of recalcitrant Micro-Exon Gene (MEG) protein from Schistosoma mansoni” employed a combination of biophysical techniques, such as circular dichroism and nuclear magnetic resonance (NMR) at natural abundance, along with in silico molecular dynamics simulations. By dividing the protein into shorter fragments, analyzing them individually, and reconstructing the complete structure, the authors successfully tackled the challenge of characterizing this elusive and highly variable protein class. Overall, the manuscript introduces a novel concept for investigating the structural information of MEG proteins, although some minor revision needed.

1. In the abstract, the authors mentioned that all isoforms of MEG 2.1 were analyzed using both biophysical and computational techniques. However, upon reviewing the manuscript, it is apparent that only isoform 1 was analyzed computationally. Therefore, the authors are advised to revise the sentences accordingly to accurately reflect the scope of their computational analysis.

2. The manuscript lacks some important figures, such as the root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) graphs of the molecular dynamics (MD) trajectory. These figures are crucial for assessing the stability of the protein structure, understanding the extent of residue fluctuations, and evaluating the structural compactness of MEG 2.1. As the manuscript focuses on the structure determination of MEG 2.1 isoforms, it is essential to discuss these results and include the corresponding figures.

3. The authors should carefully review the citation of figures within the text, particularly in the MD results and discussion section. It has been observed that some citations do not match the referenced figures, causing confusion. Therefore, the authors are advised to ensure consistency and accuracy in the citation of figures throughout the manuscript.

4. The article contains grammatical and typographical errors that require scientific editing. It is recommended that the authors carefully review the manuscript to correct these errors and enhance the overall language quality.

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Reviewer #1: No

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Divide, conquer and reconstruct: how to solve the 3D structure of recalcitrant Micro-Exon Gene (MEG) protein from Schistosoma mansoni

PONE-D-23-18239R1

Dear Dr. HOLOGNE,

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,

Ravi Pratap Barnwal, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

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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

**********

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

Reviewer #1: Yes

**********

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

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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

**********

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: All the queries have been addressed by the authors. The current form of the manuscript is suitable for publication.

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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: Dr Prateek Pandya

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