Monday, May 6, 2013

Manuscript review: Interface of the polarizable continuum model of solvation with semi-empirical methods in the GAMESS program

The review of +Casper Steinmann 's paper on PCM and semi-empirical methods is back.  First impressions

First of all it's a real pleasure to deal with an editor like this.  Second:

Accuracy
Not quite sure yet how to address this yet.  Some thoughts.  I think Chudinov et al. might have implemented D-PCM, which is not guaranteed to get the same result as C-PCM I think.  If we increase the number of tesserae do we get closer to Chudinov et al.?  Also, what is the RMSD to experiment for our implementation? Any agreement with experiment must be considered fortuitous for both Chudinov et al. and us, since both studies only consider the electrostatic part of the solvation free energy.

Numerical stability
Add at the end of 2nd paragraph in conclusions: "We therefore consider the current implementation a working code for all practical purposes, but welcome feedback from readers who encounter numerical stability problems for large molecules."

It would also be interesting to see how MOPAC performs for these systems.

Clarifications/references

**"Moreover, it is not clear to me why calculations performed with DIIS should be slower than the case with no acceleration."

We should add a sentence saying "The increase in CPU time when using DIIS is due to the extra matrix operations associated with this method, which represent the computational bottleneck for sem-empirical methods."

**"Presenting convergence tests is tedious and not generally interesting to the public, but it is mandatory if the method only converges with very tight parameters and the article only deals with the timing, scalability and implementation issues of standard methods."

When using PCM the SCF converges with all three choices of convergence acceleration.  We simply checked all three to see which one is the fastes.

**"As minor points, some of the formulas presented and the jargon adopted are not completely clear. In particular: it is not clear to me why there is a r_A in the denominator of equation (4)"

r_A is clearly defined immediately after equation (3)

**"equation (14) is not usually addressed as the PCM solvation energy, as it lacks wavefunction and geometry relaxation effects (usual PCM solvation energy is defined as the difference between the free energy of the system optimized -nuclei and electrons- in solution and the one of the system optimized in vacuum);"

We should replace "solvation energy" with "electrostatic interaction free energy"

**"it is not clear to me what STO-3G calculations refer to (perhaps Hartree-Fock calculations with STO-3G basis set?);"

We should replace "STO-3G" with "RHF/STO-3G" throughout

**"before equation (16) the authors refer to frequencies, without having introduced before what they are referring to (vibrational frequencies, computed from the diagonalization of the Hessian, as inferred from a following section);"

We should replace "frequencies" with "vibrational frequencies" right before Eq (16).

** "DIIS and SOSCF lack of a proper reference, if not of the full acronym explanation; a reference to GEPOL should be included, as all the other methods have been properly referenced."

Yes, define the acronyms and reference the methods.

----
From: PLOS ONE <plosone@plos.org>
Date: Fri, May 3, 2013 at 10:46 AM
Subject: PLOS ONE Decision: Revise [PONE-D-13-11686]
To: xxx

PONE-D-13-11686
Interface of the polarizable continuum model of solvation with semi-empirical methods in the GAMESS program
PLOS ONE

Dear Dr Steinmann,

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."

First, I must apologize for the length of time that this manuscript was under review. It was extremely difficult to find reviewers for this manuscript. Second, please ignore the reviewer's suggestion to submit to another journal. If properly revised, this work would be suitable for PLoSOne

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

1) the reviewer's comments mostly concern the clarity and motivation behind this work. Since PloSOne is not a technical computational journal, these comments must be addressed. Please provide the citations and explanations requested below.

2) the reviewer raises concerns as to whether or not the method actually works given the errors and numeric stability issues. Please provide further explanations as to the sources of these issues and in what context this could be considered a working code.

We encourage you to submit your revision within forty-five days of the date of this decision.

When your files are ready, please submit your revision by logging on to http://pone.edmgr.com/ 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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Yours sincerely,

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Academic Editor
PLOS ONE


Journal requirements:

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

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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 #2: Partly

________________________________

Please explain (optional).

Reviewer #2: The article describe the parallel implementation of a continuum-solvation scheme in combination with semi-empirical methods in a quantum-chemistry simulation package. The article is very clear, the results are reported rigorously and deficiencies of the methods have been clearly underlined. Nonetheless I would not recommend publication of this manuscript in PLOS one, as it appears to be not significantly novel with respect to other works in the literature: the
methods implemented are all standard in the quantum-chemistry literature, as well as their combination. The implementation is not deeply discussed in the text and, although showing reasonably good performances, does not appear as highly innovative, the solvation scheme considered (C-PCM) is already one of the simplest and fastest of its class. Moreover, results show deviations from a previous implementation of different authors (dating back to 1992) which are
not negligible: an error of almost 2 kcal/mol on solvation energies of the order of 60 kcal/mol is almost as big as the accuracy of the solvation model adopted. The authors suggest that numerical
differences in the implementation (cavity tessellation) are responsible for this deviation, suggesting also that their method is the one performing worse. It would have been more correct at this point to analyze the sources of such inaccuracy more in details. Similarly, some of the geometry optimizations and frequency calculations show numerical instabilities which are correctly pointed out, but not solved. Apart from the cases in which these deficiencies
only come out from the underlying algorithms in vacuum, the authors should at least have addressed more in details the numerical accuracy of the implemented method. Moreover, it is not clear to me why calculations performed with DIIS should be slower than the case with
no acceleration. Presenting convergence tests is tedious and not generally interesting to the public, but it is mandatory if the method only converges with very tight parameters and the article only deals with the timing, scalability and implementation issues of standard methods. As minor points, some of the formulas presented and the jargon adopted are not completely clear. In particular: it is not clear to me why there is a r_A in the denominator of equation (4); equation (14) is not usually addressed as the PCM solvation energy, as it lacks wavefunction and geometry relaxation effects (usual PCM solvation energy is defined as the difference between the free energy of the system optimized -nuclei and electrons- in solution and the one of the system optimized in vacuum); it is not clear to me what STO-3G calculations refer to (perhaps Hartree-Fock calculations with STO-3G basis set?); before equation (16) the authors refer to frequencies, without having introduced before what they are referring to (vibrational frequencies, computed from the diagonalization of the Hessian, as inferred from a following section); DIIS and SOSCF lack of a proper reference, if not of the full acronym explanation; a reference to GEPOL should be included, as all the other methods have been properly referenced.

________________________________

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

Reviewer #2: Yes

________________________________

Please explain (optional).

Reviewer #2: (No Response)

________________________________

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
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Reviewer #2: Yes

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Please explain (optional).

Reviewer #2: The authors use a locally modified version of an open
access quantum-chemistry code. The method of the authors is not
currently available for verification of the results, but it is
anticipated in the text that it will be available with the next code
release.

________________________________

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

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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 #2: Yes

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Please explain (optional).

Reviewer #2: Apart from a typo at the very beginning of the manuscript (page one, fourth line of the introduction "the" is repeated twice), the article is written in good comprehensible English. The jargon adopted and the acronyms are not always correctly addressed, as pointed out in the comments above. Moreover, I would avoid reporting explicitly the code keywords in the main text of the article, as is done in the computational details. As these details are important for the reproducibility of the results, I agree with the authors that they should be presented, but I would rather use the supplementary informations.

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

Reviewer #2: In general, the manuscript appears to contain good work on a very technical issue. More details on the sources of numerical instabilities and deviations from previous results would be needed to complete the reported work. These further details, which I consider necessary, would make the work even more technical. As PLOS one is not focused on the implementation of computational methods, I would suggest submission to a more specific journal.

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please include your name here (optional).

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Reviewer #2: (No Response)

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