Friday, December 13, 2013

Review of Hybrid RHF/MP2 geometry optimizations with the effective fragment molecular orbital method

The reviews of +Anders Steen Christensen and +Casper Steinmann PLoS ONE paper are in. Some preliminary thoughts:

Question 1. I think the main problem is that we left out a lot of details because they have been discussed extensively in this paper. So we need to refer to this paper more extensively.

Question 5. Reviewer #2: 
Point 1. we should clarify
Point 2. don't understand, in what way unclear
Point 3. we should make such a figure.  We shouldn't show individual fragments, but rather which parts are treated with MP2 and which parts are frozen.

From: PLOS ONE <>
Date: Wed, Dec 11, 2013 at 8:17 PM
Subject: PLOS ONE Decision: Revise [PONE-D-13-43802] - [EMID:f0cd9b87a193051a]
To: "Anders S. Christensen" <xxx>

Hybrid RHF/MP2 geometry optimizations with the effective fragment molecular orbital method

Dear Mr. S. Christensen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit, but is not suitable for publication as it currently stands. Therefore, my decision is "Major Revision." 

We invite you to submit a revised version of the manuscript that addresses the points below: 

while this manuscript presents a likely technical advance in QM/MM that could be significant, there is a lack of clarity and context in the manuscript. Each reviewer has noted different aspects that suggest a difficulty in understanding to what extent this method improves upon existing methods, and to what extent this method can be applied across multiple systems.
I encourage you to address each point made by the reviewers. The points relating to comparing this method to others and to explaining discrepancy are particularly important. This manuscript would also benefit from a reorganization and a more critical comparison to other methods.

We encourage you to submit your revision within forty-five days of the date of this decision. I recognize this might not be possible given the recommendations, so I encourage you to ask for an extension if necessary.

When your files are ready, please submit your revision by logging on to and following the Submissions Needing Revision link. Do not submit a revised manuscript as a new submission. Before uploading, you should proofread your manuscript very closely for mistakes and grammatical errors. Should your manuscript be accepted for publication, you may not have another chance to make corrections as we do not offer pre-publication proofs.

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Please also include a rebuttal letter that responds to each point brought up by the academic editor and reviewer(s). This letter should be uploaded as a Response to Reviewers file.

In addition, please provide a marked-up copy of the changes made from the previous article file as a Manuscript with Tracked Changes file. This can be done using 'track changes' in programs such as MS Word and/or highlighting any changes in the new document. 

If you choose not to submit a revision, please notify us. 

Yours sincerely, 

Academic Editor

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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: Partly

Reviewer #3: Yes

Please explain (optional).

Reviewer #1: This is relevant paper on using MP2 with effective fragment molecular orbital method and demonstrated to be alternative to ONIOM. The paper would be potentially valuable but I would suggest more discussion about the potential of the method and its outputs to be done. Chorismate mutase is the "hydrogen atom" for QM/MM modelling so there is vast majority of data from many groups, therefore there is a potential in this paper for more comprehensive discussion.

Reviewer #2: (No Response)

Reviewer #3: This study compared the EFMO method with ONIOM method as for the reaction free energy barrier for the Chorismate Mutase. In general, the results are more consistent than that of the ONIOM. This review agrees that the current manuscript is publishable, and expect the authors to explain the possible reasons for: (1) the calculated free energy barrier is much higher than that of the experimentally measured enthalpy change? (2) The authors claimed that the MP2-geometry optimization make it 3.5 kcal/mol lower for the free energy barrier than that of the ONIOM method, however, the listed data of free energy barrier in Table2 is close to each other at the same calculation level. (3) The portability to other enzyme system of EFMO method?

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

Reviewer #1: N/A

Reviewer #2: I don't know

Reviewer #3: Yes

Please explain (optional).

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: The data of all tables and figures are clean and good.

3. Does the manuscript adhere to standards in this field for data availability?

Authors must follow field-specific standards for data deposition in publicly available resources and should include accession numbers in the manuscript when relevant. The manuscript should explain what steps have been taken to make data available, particularly in cases where the data cannot be publicly deposited.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Please explain (optional).

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: This is a typical study on the topic of QM/MM method and application for enzyme reaction.

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 below.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Please explain (optional).

Reviewer #1: (No Response)

Reviewer #2: The reference should be gived as [1-13]in the text,but not [1,2,3,4,5,6,7,8,9,10,11,12,13].

Reviewer #3: Yes, the whole manuscript is organized very well, and written well.

5. Additional Comments to the Author (optional)

Please offer any additional comments here, including concerns about dual publication or research or publication ethics.

Reviewer #1: (No Response)

Reviewer #2: The authors implemented the correlated method in the EFMO/FDD approximation on the optimizing a complex of chorismate mutase and chorismate. The authors have presented the transition state structure, reaction barrier, and reaction energy, etc. While the method has more improved the results than the previous work, the paper as present is organized unclearly. There is hardly any insight that can be gained from this word. The manuscript is unsuitable for publication in current version.
To name a few questions.
1. In the theory part, the given molecular system is described, which is defined into tow domains F and A. But in the following description, the b domain (buffer domain) is contained. The system is divided into three domains or two domains? 
2. The Table 1 and 2 is disordered.
3. The complex which divided into different domains should show in a figure, which describes the structure and thedevision of different domains in the complex of chorismate mutase and chorismate. It makes the computed model direct and clear.

Reviewer #3: no additional comments at this time.

6. If you would like your identity to be revealed to the authors, please include your name here (optional).

Your name and review will not be published with the manuscript.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: (No Response)
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