PCOMPBIOL-D-24-01810mdciao: Accessible Analysis and Visualization of Molecular Dynamics Simulation DataPLOS Computational Biology Dear Dr. Pérez-Hernández, Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology'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 within 60 days Jan 25 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 ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ 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 editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.* 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, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. We look forward to receiving your revised manuscript. Kind regards, Alexander MacKerellAcademic EditorPLOS Computational Biology Arne ElofssonSection EditorPLOS Computational Biology Feilim Mac GabhannEditor-in-ChiefPLOS Computational Biology Jason PapinEditor-in-ChiefPLOS Computational Biology  Journal Requirements:

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 Reviewers' comments: Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: review is uploaded as an attachment

Reviewer #2: Pérez-Hernández and Hildebrand report an elegant ethod to conveniently analyze Md trajectories with particular focus on inter-residue (or residue-ligand) contact mapping. It delivers a number of very useful, high resolution plots, allowing easily to compare systems (i.e. with different ligands, with mutations), particularly-but not limited to- on the cases of GPCRs, G-proteins ir kinases, as it adapts the standard nomenclature on those cases. A limitation that is conveniently outlined by the authors is the lack of decomposing on atom-residue mapping, probably more suited to drug-design projects, but the scope of mdciao is clearly stated to be on the protein-protein interactions (inter or intraprotein) and as such it is a very complete method.

The software installs easily, it is also available on-line, very well documented with a number of examples of e-g- jupyter-notebooks that can be used as a starting point for novel users.

I have only a few minor corrections of typos or grammar as follows:

- line 41- "MDanalysis, The API" replace comma by dot

- line 153 - "a growing list works " probably "a growing list OF works (studies?)"

Reviewer #3: The manuscript “mdciao: Accessible Analysis and Visualization of Molecular Dynamics Simulation Data” by Perez-Hernandez and Hildebrand presents a software, actually command line tools and a python API, for analysis and representation of molecular dynamics (MD) simulation data. While many programmes exist to analyse and/or visualise MD data, including python modules rich in functionality, the authors claim to fill a gap by catering to non-expert users (with production-ready tables and figures) and expert users alike (by full flexibility to use the API in their python workflow).

The software is indeed useful and the description and examples provided in the present manuscript provide a good overview and introduction into its functionality, in particular thanks to the access to worked examples.

However, a few things need to be improved in the manuscript:

In the list of the added values, the authors mention, among others,

“residue-residue contact-frequencies with hard cutoffs” as an easy and universal metric.

However, it is not fully explained why this is desirable as the most important , if not only (?) metric, in the first place.

The authors discuss that such contacts defined via a hard cut-off are preferable over more fine-tuned parameters and should therefore be transferable. Given the importance of the contacts and the corresponding cut-off, it should be detailed more in the methods section of the manuscript. That is which of the “typically 3.5-4.5A” is chosen (say, as user-friendly default)? To which atoms does this distance cutoff apply? To all atoms of two residues in question? Only heavy atoms? The nearest two?

Furthermore, the authors claim to “special care on user-friendliness, documentation (inline and online) and tutorials”. The first can be tested by only using the software – and appears to be achieved for this reviewer. Documentation and tutorials are provided as example notebooks, or learning command line tools, and these are highly appreciated.

The link to documentation and tutorials should be placed more prominently in the manuscript, perhaps even in the abstract close to the link to the github repository.

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes:  Adithya Polasa

Reviewer #2: Yes:  Hugo Gutiérrez-de-Terán

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Review of Mdciao.docx

Dear Dr. Pérez-Hernández,

We are pleased to inform you that your manuscript 'mdciao: Accessible Analysis and Visualization of Molecular Dynamics Simulation Data' has been provisionally accepted for publication in PLOS Computational Biology.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Alexander MacKerell

Academic Editor

PLOS Computational Biology

Arne Elofsson

Section Editor

PLOS Computational Biology

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