Wednesday, May 22, 2013
Sunday, May 19, 2013
New manuscript: Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics
+Anders Steen Christensen's study on protein structure validation is now on arXiv. It was submitted to PNAS but was rejected without review. So now we are trying JACS.
Here is the abstract:
We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3JNC') spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to refine protein structures to this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.
Here is the abstract:
We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3JNC') spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to refine protein structures to this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.
Why is life chiral?
Ingeniøren, the magazine of the Danish society for engineers, has a column where people submit questions, which are then farmed out to scientists who provide short answers.
The question send to me is (translated from Danish)
This is not known but there is some speculation, which can be divided into two general categories: When life began, there were (1) a greater concentration of biologically relevant molecules with the mirror image form that are now found in living organisms, and (2) equal concentrations of mirror-image forms, and the mirror-image form we see now in living organisms was chosen by chance and then copied.
Category 1: It came from outer space
Amino acids with a higher concentration of the mirror-image form that is now found in living organisms have been found in meteorites on Earth. So if a sizable part of life's building blocks came from space, this may be the answer.
The reason for this difference in concentration is likely to result from chemical reactions in space that are affected by "polarized" light from the stars. Light comes also two mirror-image forms and starlight has a little bit more of one kind. This is called polarized light, which kan affect chemical reactions in such a way that as to form more of one mirror-image form than the other. The light must travel long distances to be polarized so that the sunlight that hits the Earth is not polarized.
Beta-decay, a sort of natural radioactive radiation, can also lead to polarized light here on earth, but it is uncertain whether the amount of light is enough to have a practical effect on chemical reactions.
Category 2: That's life
Because the genetic code is the same in all organisms, we assume life as we know it may lead back to a single "primordial cell", as it is unlikely that such a complex system can be created randomly twice. Whether the the reason for this is that life originated only once, or whether this cell happened to survived where other cells (in other biochemical ways to copy object) died, is not known.
The same considerations apply to the molecules and reactions which underlie life. We know that many molecules of the same mirror-image form "clumps together" and that many self-replicating molecules retain their mirror image form. It is therefore possible that a group of molecules of the same mirror-image form by chance clumped together in such a way that they can make copies of themselves, and this is the basis of our primordial cell. If this only happened on one occasion, it may explain why we only see a mirror image form in living organisms.
The question send to me is (translated from Danish)
Chemical substances are found in two variants which are each other's mirror image. In an ordinary chemical reaction in the laboratory, there is formed the same amount of the two mirror image forms. In the natural products and organisms there are only one of the two mirror image forms. Why is there only one mirror-image form of natural substances and living organisms?Once you know the term for this (homochirality) there is plenty of information on the web, including a wiki page. Here's me trying to get my head around some of it and explain it in layman's terms. Comments welcome.
This is not known but there is some speculation, which can be divided into two general categories: When life began, there were (1) a greater concentration of biologically relevant molecules with the mirror image form that are now found in living organisms, and (2) equal concentrations of mirror-image forms, and the mirror-image form we see now in living organisms was chosen by chance and then copied.
Category 1: It came from outer space
Amino acids with a higher concentration of the mirror-image form that is now found in living organisms have been found in meteorites on Earth. So if a sizable part of life's building blocks came from space, this may be the answer.
The reason for this difference in concentration is likely to result from chemical reactions in space that are affected by "polarized" light from the stars. Light comes also two mirror-image forms and starlight has a little bit more of one kind. This is called polarized light, which kan affect chemical reactions in such a way that as to form more of one mirror-image form than the other. The light must travel long distances to be polarized so that the sunlight that hits the Earth is not polarized.
Beta-decay, a sort of natural radioactive radiation, can also lead to polarized light here on earth, but it is uncertain whether the amount of light is enough to have a practical effect on chemical reactions.
Category 2: That's life
Because the genetic code is the same in all organisms, we assume life as we know it may lead back to a single "primordial cell", as it is unlikely that such a complex system can be created randomly twice. Whether the the reason for this is that life originated only once, or whether this cell happened to survived where other cells (in other biochemical ways to copy object) died, is not known.
The same considerations apply to the molecules and reactions which underlie life. We know that many molecules of the same mirror-image form "clumps together" and that many self-replicating molecules retain their mirror image form. It is therefore possible that a group of molecules of the same mirror-image form by chance clumped together in such a way that they can make copies of themselves, and this is the basis of our primordial cell. If this only happened on one occasion, it may explain why we only see a mirror image form in living organisms.
Saturday, May 18, 2013
Taking a chemistry MOOC - part 1
The massively online open course (MOOC)
I, along with almost 8000 other people, am taking Chris Cramers' MOOC Statistical Molecular Thermodynamics, which is officially starting Monday. I am curious how a MOOC works in practice So and what Chris chooses to focus on.
Step 1 is to sign up and get a login to the course, which gets you access to the course material. I signed up in February, but haven't gotten an email yet about the fact that the course material is available. Good thing I follow Chris on twitter.
So far material for the first 3 weeks are available. The topic for week 1 is quantization and energy levels. The material for week 1 consists of 8 video lectures (between 8 and 16 minutes each) with corresponding powerpoint slides, and a homework assignment with 10 multiple choice questions. Five of the videos have one or more multiple choice questions embedded in them, and you can also download detailed answers to these questions.
"The videos are the core content of this course." The idea, according to the website, it is "that you download the homework pdfs and familiarize yourself with the questions early on. As you view the videos, keep the homework problems in front of you so that you can make connections between the lectures, the demonstrations and the problems."
Once you have finished the homework you submit it on the web site. The deadline for submission for week 1 is May 31st, and the answers become available the next day. Update: when you submit your answers, you are immediately told whether it is right or wrong. Also, this week, remember not to confuse De with D0 (happened to a friend of mine ...)
There is also a discussion forum, monitored by instructors.
Some thoughts
Chris made the videos, slides and homework problems. What does Coursera provide? (1) A website that keeps track of users responses to the homework (and later the final exam) needed for the certificate you get at the end and (2) a way to embed multiple choice questions in a video.
If one is not issuing certificates, I'm not sure Coursera is needed, but this is only a first impression. Embedding quizzes in videos can be solved by shorter videos that end in a quiz, i.e. watch this video, then answer this question.
From a teachers perspective I think the main practical difference between regular teaching and a MOOC (as exemplified by this course) is that you don't rely on a textbook with regard to reading and assignments (in addition to making all the videos of course).
I'm not sure how I feel about using Powerpoint lectures vs pencasts. Powerpoint can go a bit fast, but here you can rewind and you get a written record of the lecture through the slides.
I, along with almost 8000 other people, am taking Chris Cramers' MOOC Statistical Molecular Thermodynamics, which is officially starting Monday. I am curious how a MOOC works in practice So and what Chris chooses to focus on.
Step 1 is to sign up and get a login to the course, which gets you access to the course material. I signed up in February, but haven't gotten an email yet about the fact that the course material is available. Good thing I follow Chris on twitter.
So far material for the first 3 weeks are available. The topic for week 1 is quantization and energy levels. The material for week 1 consists of 8 video lectures (between 8 and 16 minutes each) with corresponding powerpoint slides, and a homework assignment with 10 multiple choice questions. Five of the videos have one or more multiple choice questions embedded in them, and you can also download detailed answers to these questions.
"The videos are the core content of this course." The idea, according to the website, it is "that you download the homework pdfs and familiarize yourself with the questions early on. As you view the videos, keep the homework problems in front of you so that you can make connections between the lectures, the demonstrations and the problems."
Once you have finished the homework you submit it on the web site. The deadline for submission for week 1 is May 31st, and the answers become available the next day. Update: when you submit your answers, you are immediately told whether it is right or wrong. Also, this week, remember not to confuse De with D0 (happened to a friend of mine ...)
There is also a discussion forum, monitored by instructors.
Some thoughts
Chris made the videos, slides and homework problems. What does Coursera provide? (1) A website that keeps track of users responses to the homework (and later the final exam) needed for the certificate you get at the end and (2) a way to embed multiple choice questions in a video.
If one is not issuing certificates, I'm not sure Coursera is needed, but this is only a first impression. Embedding quizzes in videos can be solved by shorter videos that end in a quiz, i.e. watch this video, then answer this question.
From a teachers perspective I think the main practical difference between regular teaching and a MOOC (as exemplified by this course) is that you don't rely on a textbook with regard to reading and assignments (in addition to making all the videos of course).
I'm not sure how I feel about using Powerpoint lectures vs pencasts. Powerpoint can go a bit fast, but here you can rewind and you get a written record of the lecture through the slides.
Thursday, May 9, 2013
Frontiers in Theoretical and Computational Chemistry
I was recently invited to be a "Review Editor" for Frontiers in Theoretical and Computational Chemistry. One of the commendable features of FTCC is that the reviews are done by a board review editors and the names of these reviewers are displayed on the published manuscript. I sign all my reviews already, so I think that's an excellent idea. In fact I think they should publish the reviews too.
FTCC is also open access, publishes under the CC-BY license, arXiv-friendly and "significance" is not a review criterion. So what's not to like? Well, the publishing fee is a bit steep: €1600 (though it may be possible to get a fee waiver). Considering the considerably lower fees at PeerJ or even PLoS ONE the size of this fee is a result either of inefficiency or avarice (FTCC is owned by the Nature Publishing Group). But as the fees appear to have been set before NPG took over, it looks like it's just inefficiency.
So I have decided to accept and I might even submit a paper there if I can get a partial fee waiver or land a big grant.
FTCC is also open access, publishes under the CC-BY license, arXiv-friendly and "significance" is not a review criterion. So what's not to like? Well, the publishing fee is a bit steep: €1600 (though it may be possible to get a fee waiver). Considering the considerably lower fees at PeerJ or even PLoS ONE the size of this fee is a result either of inefficiency or avarice (FTCC is owned by the Nature Publishing Group). But as the fees appear to have been set before NPG took over, it looks like it's just inefficiency.
So I have decided to accept and I might even submit a paper there if I can get a partial fee waiver or land a big grant.
Sorry Inorganic Chemistry: I only review for arXiv-friendly journals
From: Jan Halborg Jensen
Sent: Thursday, May 02, 2013 12:38 PM
To: xx
Subject: Re: Invitation to Review Manuscript ic-2013-xx
Dear xx
Does Inorganic Chemistry consider paper that have been deposited on the preprint server arXiv? I ask because I am boycotting (i.e. not reviewing for or submitting to) all journals that don't.
Best regards, Jan
-----
From: xxx
Sent: Friday, May 03, 2013 10:21 PM
To: Jan Halborg Jensen
Subject: Re: Invitation to Review Manuscript ic-2013-xxx
Prof. Jensen, Our policy with regards to arXiv is as follows:
If a submission to IC is essentially the same as a preprint in arXiv, then it will not be considered for publication, but if it differs significantly (and contains significant new work), then it will be considered.
I hope this answers your question.
xxx
IC Journal office
----
From: xx
Sent: Thursday, May 09, 2013 7:48 AM
To: Jan Halborg Jensen
Subject: Reminder: Inorganic Chemistry
09-May-2013
Dear Dr. Jensen:
Recently, I invited you to review Manuscript ID ic-2013-xx. I have yet to hear from you about this.
This e-mail is simply a reminder to respond to the invitation to review. I appreciate your help in accomplishing our goal of having an expedited reviewing process. Please do not hesitate to contact me if I can be of any assistance.
Sincerely,
xx
-------
From: Jan Halborg Jensen
Sent: Thursday, May 09, 2013 10:25 AM
To: xx
Subject: RE: Reminder: Inorganic Chemistry
Dear xx
I am afraid I won't be able to review this paper, because I find Inorganic Chemistry's policy with regard to pre-print deposition on arXiv too restrictive and not in the best interest of science. I urge you to re-consider this policy, in which case I would be happy to serve as a reviewer.
Best regards, Jan
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.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.
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,
xxx
Academic Editor
PLOS ONE
Journal requirements:
When submitting your revision, we need you to address these additional
requirements.
1. Please include a copy of Supplementary Figure S1 which you refer to
in your text.
[Note: HTML markup is below. Please do not edit.]
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
the data cannot be publicly deposited.
Reviewer #2: Yes
________________________________
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?
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 #2: Yes
________________________________
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.
________________________________
5. Additional Comments to the Author (optional)
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.
________________________________
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 #2: (No Response)
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.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.
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,
xxx
Academic Editor
PLOS ONE
Journal requirements:
When submitting your revision, we need you to address these additional
requirements.
1. Please include a copy of Supplementary Figure S1 which you refer to
in your text.
[Note: HTML markup is below. Please do not edit.]
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
the data cannot be publicly deposited.
Reviewer #2: Yes
________________________________
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?
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 #2: Yes
________________________________
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.
________________________________
5. Additional Comments to the Author (optional)
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.
________________________________
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 #2: (No Response)
Subscribe to:
Posts (Atom)