Peer Review History

Original SubmissionNovember 1, 2024
Decision Letter - Daniel Ioan Hunyadi, Editor

PONE-D-24-49897Bio-Inspired Cryptography Based on Proteinoid AssembliesPLOS ONE

Dear Dr. Mougkogiannis,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 12 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Daniel Ioan Hunyadi, Ph.D.

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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3. Thank you for stating the following financial disclosure: [y EPSRC Grant EP/W010887/1 “Computing with proteinoids”]. 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." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: I Don't Know

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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

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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

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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: Title- Bio-Inspired Cryptography Based on Proteinoid Assemblies

1. Justify the statement " Bioinspired cryptography has emerged as a significant area of research,".

2. The table 1 compare the bio inspired cryptography and key based cryptography, what is the need of both of the approach.

3. materials and methods section is too small, i have a suggestion to add more data from the result section.

Reviewer #2: This paper seems to have some innovative scientific crypto contribution benefiting from deterministic interactions of proteinoid assemblies. The work generates secure encryption keys for algorithms using unpredictability of proteinoid behaviour that is considered adaptable encryption framework resisting known cryptanalytic attacks. The exploration illustrates the implementation of bio-inspired system based on simulated proteinoid interactions resulting promissing encryption strength. The research show random key generation presenting security of standard statistical tests immune to classical and quantum computers attacks. This study innovates security via biological principles of potential processes in cryptography needing overall secrecy reconsideration in order to be in ready and complete. Therefore, the following secrecy references are recommended to be involved:

== “AI Based Mobile Edge Computing for IoT: Applications, Challenges, and Future Scope”, Arabian Journal for Science and Engineering (2022). http://doi.org/10.1007/s13369-021-06348-2

== "Personal Privacy Evaluation of Smart Devices Applications Serving Hajj and Umrah Rituals", Journal of Engineering Research (2021). http://doi.org/10.36909/jer.13199

== "Cybercrime on Transportation Airline", Journal of Forensic Research, ISSN: 2157-7145, 10(4):449 (2019)

== "Sensing e-Banking Cybercrimes Vulnerabilities via Smart Information Sciences Strategies", RAS Engineering and Technology 1(1):1-9 (2020)

== "Engineering Graphical Captcha and AES Crypto Hash Functions for Secure Online Authentication", Journal of Engineering Research (2021). http://doi.org/10.36909/jer.13761

The work is more interesting if considering the following image hiding strategies proposed within below encryption researches:

== "Varying PRNG to improve image cryptography implementation", Journal of Engineering Research 9(3A):153-183 (2021).

== "Remodeling Randomness Prioritization to Boost-up Security of RGB Image Encryption", Multimedia Tools and Applications (MTAP) 80(18):28521–28581 (2021)

== “Dynamic smart random preference for higher medical image confidentiality”, Journal of Engineering Research (2022) http://doi.org/10.36909/jer.17853

== "Improving data hiding within colour images using hue component of HSV colour space", CAAI Transactions on Intelligence Technology, 7(1): 56–68 (2022)

== "Efficient Image Reversible Data Hiding Technique Based on Interpolation Optimization", Arabian Journal for Science and Engineering (AJSE) 46(9):8441–8456 (2021)

== "Efficient Reversible Data Hiding Multimedia Technique Based on Smart Image Interpolation", Multimedia Tools and Applications (MTAP) 79(39):30087-30109 (2020)

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6. 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: Sultan H. Almotiri

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

response to reviewers letter attached!

Attachments
Attachment
Submitted filename: Response_to_Reviewers.pdf
Decision Letter - Daniel Ioan Hunyadi, Editor

PONE-D-24-49897R1Bio-Inspired Cryptography Based on Proteinoid AssembliesPLOS ONE

Dear Dr. Mougkogiannis,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Feb 28 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Daniel Ioan Hunyadi, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

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 #3: All comments have been addressed

Reviewer #4: (No Response)

Reviewer #5: (No Response)

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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 #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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

Reviewer #3: N/A

Reviewer #4: Yes

Reviewer #5: 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 #3: No

Reviewer #4: No

Reviewer #5: 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 #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #3: This paper proposed a new cryptographic method by taking advantage of the unpredictability of protein-like behavior. It used simulated protein-like interactions to realize a bionic system, and the results met the current encryption strength standards and also had advantages in key generation and distribution. This paper has a clear structure and complete content, but there are still the following problems.

1�� The cryptographic primitive proposed in this paper is innovative, but lacks theoretical proof of its security. This paper proposed that the security of the cryptographic algorithm depends on the unpredictability of the key generated based on protein-like capacitors. However, the ciphertext after encoding and encryption still has certain statistical characteristics. The security of this part lacks corresponding proof and analysis.

2�� There is a lack of evidence and analysis on the unpredictability of keys generated based on protein-like capacitors. For example, do different protein-like proteins have similar capacitance values? Is there a relatively fixed numerical relationship between capacitance and the chemical composition, structural characteristics, and polymerization mode of protein-like proteins?

3�� There is a problem with the image layout, and the corresponding image cannot be indexed.

Reviewer #4: (No Response)

Reviewer #5: Provide more detailed explanations of how proteinoid assemblies specifically interact with cryptographic algorithms.

This would make the biological inspiration clearer and more accessible for readers unfamiliar with proteinoids.

Include a comparison table between proteinoid-based cryptography and traditional encryption methods in terms of efficiency, security, and scalability. This could highlight the advantages and unique aspects of the bio-inspired approach.

Explore ways to optimize the proteinoid-based encryption system for real-time applications.

Include a broader range of test cases and attack simulations, especially those involving different types of quantum and classical attacks, to strengthen the claim of robustness.

Suggest the potential for further collaboration with biologists, material scientists, and cryptographers to refine proteinoid-based systems and explore additional biological processes for future cryptographic improvements.

All figures looks blurry and not clearly visible to depict the findings.

Discuss how the proteinoid-based encryption can be integrated into existing security frameworks or protocols to assess compatibility and ease of adoption in current cryptographic infrastructures.

Address the potential environmental and cost benefits or challenges in producing proteinoids for widespread use in cryptography.

Proof read the paper and correct grammatical errors through out the work.

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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 #3: No

Reviewer #4: No

Reviewer #5: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments
Attachment
Submitted filename: Recommendation.docx
Revision 2

Dear Editor,

The response to the reviewers is attached as a PDF file.

Thanks,

The authors

Attachments
Attachment
Submitted filename: Respnse to reviewers.pdf
Decision Letter - Daniel Ioan Hunyadi, Editor

PONE-D-24-49897R2Bio-Inspired Cryptography Based on Proteinoid AssembliesPLOS ONE

Dear Dr. Mougkogiannis,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 26 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Daniel Ioan Hunyadi, Ph.D.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

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 #6: All comments have been addressed

Reviewer #7: 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 #6: No

Reviewer #7: No

**********

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

Reviewer #6: No

Reviewer #7: No

**********

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 #6: No

Reviewer #7: No

**********

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 #6: No

Reviewer #7: No

**********

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 #6: In principle, a process that is not replicable in the same way, with the same values is random and one that generates uncorrelated output values, but which can be replicated by knowing some parameters of the generation algorithm, will produce a pseudorandom set. From the description made, the primary model from which the authors start could be one used for random systems. The applicability would be limited by the transmission model of these data sets, called seeds in cryptography, and used within pseudorandom models, as initial values of the system.

To get out of this scope of applicability, which does not allow the correlation of the emitter and the receiver in order to fulfill the fundamental axiom of a cryptographic system, the authors should illustrate the completeness of the proposed model. In this sense, it would be useful:

1. A dedicated section to clearly illustrate how the correlation of keys from the sender of the encryption data system to the receiver of the encrypted data is achieved, in order to fulfill d(e(m))=m?

2. A clear and mathematically substantiated explanation for a correlative question with the applicability of the proposed solution: why do the electrical properties of proteinoids provide mathematical security comparable to traditional methods (AES, RSA, etc.)?

3. How is it ensured that an attacker cannot replicate a set of proteinoids and generate the same keys?

4. The key generation algorithm is based on measurable physical values, but experimental variability could affect the reproducibility of the keys. How is the synchronization of the two parties involved in communication achieved? And in this sense, the correlation of these explanations with point 3.

Reviewer #7: A process that cannot be reproduced in the same way and with the same initial values can be considered random, since it does not show determinism in its evolution. In contrast, a system that generates uncorrelated output values, but which can be replicated by knowing specific parameters of the generation algorithm, produces a pseudorandom sequence. From the description provided, the fundamental model proposed by the authors seems to be usable in systems with a random character. However, its applicability could be limited by the mechanism for distributing these data sets, called seeds in cryptography, essential in pseudorandom algorithms, where they are used as initial values to determine the behavior of the system. If the authors want to choose this way of generating cryptographic primitives, perhaps a study that would use the values generated for the seed of models derived from authenticated Diffie-Helmann would be more useful.

To clarify the sustainability of the proposed solution, especially in the context where, if functional, the proposed method would be an idea that should revolutionize the way cryptographic systems can be built, it would be useful to consider the following:

1. A dedicated section describing the limitations of the method and describing possible mitigation methods.

2. Table 1 provides a comparison between different cryptographic technologies; however, for a more rigorous evaluation, it would be necessary to include quantitative criteria, such as system performance, security level, computational complexity or energy efficiency.

3. Clarify and rigorously detail the mechanisms by which proteinoids constitute a viable cryptographic solution, highlighting the aspects that give them security, robustness and practical applicability compared to traditional cryptographic methods.

4. Provide a detailed and rigorous analysis of the entropy and security level of the generated keys, highlighting the degree of randomization, resistance to cryptanalytic attacks and their compliance with current security standards.

5. A review of the abstract and introduction would be useful to explain more clearly, beyond a narrative presentation, how the proposed solution is built and how it works.

6. The completeness and synchronization of the key models and algorithms used by the sender and receiver.

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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 #6: No

Reviewer #7: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 3

Dear Editor

The response to reviewers document has been attached in previous step.

Thanks

The Authors

Attachments
Attachment
Submitted filename: PONE-D-24-49897R2.pdf
Decision Letter - Daniel Ioan Hunyadi, Editor

Bio-Inspired Cryptography Based on Proteinoid Assemblies

PONE-D-24-49897R3

Dear Dr. Mougkogiannis,

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.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Daniel Ioan Hunyadi, 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 #6: All comments have been addressed

Reviewer #8: All comments have been addressed

**********

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 #6: Yes

Reviewer #8: Yes

**********

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

Reviewer #6: Yes

Reviewer #8: 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 #6: No

Reviewer #8: Yes

**********

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 #6: Yes

Reviewer #8: 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 #6: The current version of the article deals with the subject addressed in a clear way and has responded fairly enough to all the comments made.

In this form the article describes clearly enough the proposed cryptographic technique. Even if the real applicability of the proposed solution has certain functional implementation problems, from a purely theoretical point of view of the study this can be considered a research article.

Reviewer #8: The authors have significantly improved the manuscript over the course of the three revisions. The final version presents a compelling integration of biological principles with cryptographic innovation, specifically through the use of proteinoid assemblies. The experimental design has become clearer, and the encryption methodology—particularly the translation of electrical capacitance into secure key generation—is now articulated with better precision. The statistical validation of key randomness, the complexity analysis, and the energy efficiency metrics help substantiate the claims made. Some minor linguistic polishing could further improve the readability of the paper, but overall, the manuscript has matured into a coherent and original contribution to the field of bio-inspired cryptography. I recommend it for publication.

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Reviewer #6: No

Reviewer #8: Yes: AMJED ABBAS

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Formally Accepted
Acceptance Letter - Daniel Ioan Hunyadi, Editor

PONE-D-24-49897R3

PLOS ONE

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