The end of a saga: "In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB" accepted in PeerJ

The reviews for Martin's last paper (which we submitted 28 days ago) came back July 31st and can be found below.  Before I could even present them in a blogpost Martin had a response ready, which was sent in late yesterday and promptly accepted (I am glad I managed to upgrade before that happened!).

When I say the end of a saga here is what I mean:

The paper is submitted to arXiv Sept 20, 2012 (almost a year ago)
The papers is rejected without review by JCIM and PCCP
Journal of Molecular Catalysis B: get your act together
Original PLoS ONE reviews
Our rebuttal
The rejection
Our appeal

Our appeal is rejected

Anyway, I am really happy the paper found a home at +PeerJ, especially considering the only remaining alternative.

Review:

Thank you for your submission to PeerJ. I am writing to inform you that in my opinion as the Academic Editor for your article, your manuscript "In silico screening of 393 mutants facilitates enzyme engineering of amidase activity in CalB" (#2013:07:643:0:0:REVIEW) requires some minor revisions before we could accept it for publication.

The comments supplied by the reviewers on this revision are pasted below. My comments are as follows:

Editor's comments

Please address critical points raised by the first reviewer.

If you are willing to undertake these changes, please submit your revised manuscript (with any rebuttal information*) to the journal within 45 days.

* A rebuttal letter and any tracked changes can be added to the file uploads page under the "Revision response files" section. Please also upload a clean untracked version for production purposes to the primary files section and replace your previous manuscript. Accepted formats for the rebuttal letter and tracked changes are: docx (preferred), doc, and PDF.

xxx 

Academic Editor for PeerJ

Reviewer Comments

Reviewer 1

Basic reporting

No Comments

Experimental design

No Comments

Validity of the findings

No Comments

Comments for the author

This manuscript describes in silico screening of CalB mutants for enzymatic amidase activity. Then the computational results are benchmarked against experimental studies. The computational approach gives reasonable results in general -- the authors demonstrate that 15 out of 22 mutants are correctly predicted in qualitative activity. The manuscript is scholarly and well written. The methods are complete and clear. The data are new and appear to be true. I recommend publishing with minor revision.

I have a few minor suggestions/questions.

1. In table 1, two columns are both labeled with “Cat.” The authors need to make more detailed labels to distinguish (one from Exp. and the other is from Calc.). Also, the authors need to include the cutoff of 12.5 kcal/mol in the table legends otherwise it is difficult for readers to correlate calculated barriers with calculated cat.

2. In pg. 8, the authors state that the cutoff is done purely for a post hoc comparison of experimental and computed data. And they used 12.5 kcal/mol as cutoff. The authors need to expand this section to give detailed descriptions about how they reach the value of 12.5 in their study.

3. For results and discussion part, the two subtitles are “Set S” and “Set L”. It might be useful to guide readers if the authors can use more detailed subtitles which can generally summarize their results.

4. In the last part of results and discussion, the authors state that I189G as a single mutant is counterproductive but lowers the barrier of G39A-A141Q-L278A. This would suggest there are couplings between I189 and G39/A141/L278. While it is difficult to figure out such kind of couplings, one simple question is, is I189 close to G39/A141/L278 in the structure.

Reviewer 2

Basic reporting

Meets all necessary criteria

Experimental design

Excellent

Validity of the findings

Excellent

Comments for the author

This is an excellent paper, nicely demonstrating the utility of a practical computational modelling approach to the prediction of enzyme activity. The method uses semiempirical quantum chemical methods to model amidase reactivity in a lipase. This is thorough work of high quality. The paper is well written and the results are analysed and presented in appropriate detail. The results will be of wide interest. This is a demonstration of a method that will find real industrial application, as well as in other contexts. The paper is suitable for publication essentially as is. A minor point is that some of the references might be lacking information (e.g. refs 27 and 28 do not look complete as written). Also, the authors might want to comment a little more on how amidase activity is achieved. There is wide debate about amidase versus esterase activity, and, while this is not the focus here, comparison with enzymes such as fatty acid amide hydrolase, which has been the subject of much modelling work, could be useful (e.g. a little more discussion on what specific features may provide amidase activity and how the designed amidases compare to natural amidaases). This could assist in future rational design (as well as in testing the quantum chemical methods by comparisons on related reactions.

Open access licenses: It's all about reuse - part 2

This post is a response to this post by Rosie Redfield.

"It's time for open-access advocates and especially publishers to take on the responsibility of informing authors of all the consequences, not just the good ones."

I think this is the fundamental disconnect in the discussion.  I think most OA advocates on-balance don't see the commercial use of OA content allowed by the CC-BY as a bad thing.  I don't think the "The authors shouldn't see this as harmful" responses you mention in your comments are blaming the authors.  Rather, people are trying to tell them something important about the fundamental motivation behind OA: gratis vs libre (http://www.sparc.arl.org/resource/gratis-and-libre-open-access).  Are you just free to read the paper or can you do something with it?

If you really think about it any license but CC-BY (or CC0) place severe (and often unexpected) limitations on use.

Some examples: publishing under CC-BY-NC means that figures cannot be used in textbooks, course packs for sale at the bookstore, blogposts on http://rrresearch.fieldofscience.COM/, lecture notes for students paying for the signature track in this MOOC: https://www.coursera.org/course/usefulgenetics, any company that charges anything at all to cover the cost of distributing papers on DVDs to regions with poor internet connections, and, most important, hundreds of other good uses no-one has thought of yet.
     
Publishing under CC-BY-SA means that if you use a single figure from such a paper in your lecture notes, then you must license your notes under CC-BY-SA.  The same goes for using a CC-BY-SA image on a blogpost.  One could make a good argument for the fact now you have to license your entire blog under that license.  This is why CC-BY-SA is called a viral license: a single instance of use "infects" the site/file/book/course and "spreads" the license.  For people who don't want to license their work under the CC-BY-SA license, work published under the CC-BY-SA license is hard to use.

CC-BY (or CC0) removes these problems, so your reasons for using anything else have better be well thought-through.*  I would be very interested in some detailed reasons for why having your OA article included in a compendium by a commercial publisher is a bad thing and why stopping that from happening outweighs other problems associated with licenses other than CC-BY or signing your copyright away.

*That includes signing your copyright over to commercial publishers (i.e. when authors "rethink their use of open-access").  Try to ask permission to use a figure from such a publication for much of anything and you'll find that these figures are very much for sale by commercial publishers, without asking authors (why? they don't have copyright) and for a lot more than $80.


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Martin's latest paper is 'Featured Article' on PeerJ

Martin's paper has been recently accepted in PeerJ, and it is now showcased as 'Featured Article' on the journal web page. Way to go!

The article is available here.

Commercial reuse of published scientific papers: It's all about reuse

Two books have been recently discussed quite vigorously online: A Rant on Strawberries, Open Access Licenses and the Reuse of Published Papers and Apple Academic Press: Predatory publisher of scholarly books.  The publisher Apple Academic Press (Apple AP) combines freely available open access articles on a common topic into books, which sell for about $100.  Without informing the authors of the papers.

In the first book no citations to the articles appeared anywhere in the book (Apple AP claims that this was a mistake) and in the second the references where given at the end of the book under "Authors Notes".  Much has been written about how sleazy it is in comparison to what commercial publishers do.

However, two important comments in the original blog posts have, in my mind, not really been discussed.

C.W. Schadt writes:

Anyway, Im not sure who to be more upset with.  The editor and publisher that (re)published the article, or myself for not noticing the reuse clause in the open access license.  From now on I vow that I will pay closer attention to this, and it may influence where I end up submitting future papers.

Rosie Redfield writes:

My colleague and her co-authors are outraged; they had no idea that this commercial reuse was permitted by the standard agreements.  In principle the authors should have read the fine print, but as advocates of open-access publishing I think the onus is on us to make sure that the copyright agreements are in accord with authors' reasonable expectations and wishes.

To me this sounds like both fundamentally disagree with the commercial reuse granted by the CC-BY license used by the journals and would rather publish under the CC-BY-SA or CC-BY-NC license.  I hope I am wrong; but in case I am not: publishing under anything other than CC-BY or CC0 is really bad for science and society.  Here are some reasons why:

What is a viral license?
CC-BY and licences; we must not get it wrong. I offer some clarification
Why CC-BY? 

I think this quote sums it nicely:

This just won’t do. It’s not open access. To quote Heather Piwowar’s pithy statement once more, “We do basic research not only to know more, but to do more”. Non-commercial licences impede the use of research, and that’s not to the benefit of wider society.

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Excellent advice on teaching from Carl Wieman

I recently came across to excellent sources for teaching advice.  One is an article by Carl Wieman in Change Magazine called Why Not Try a Scientific Approach to Science Education?  The other is the Instructor Guidance page from the Carl Wieman Science Education Initiative at UBC. 

On the latter page I specifically want to highlight two links (to pdf files):

What Not To Do; Practices that should be avoided when implementing active learning 

Preclass-Reading Assignments; Why they may be the most important homework for your students

In the latter link I especially like Best Practice number 2:

Omit everything that is not necessary. The shorter the assignment is, the more likely the students will actually read it and focus on the key material. Some instructors believe in longer, less focused, readings from which the students are expected to extract the relevant material. This is an unrealistic expectation for a first exposure to the material.

This point is discussed further in Why Not Try a Scientific Approach to Science Education:

Reducing Cognitive Load
The first way in which one can use research on learning to create better classroom practices addresses the limited capacity of the short-term working memory. Anything one can do to reduce cognitive load improves learning. The effective teacher recognizes that giving the students material to master is the mental equivalent of giving them packages to carry. With only one package, they can make a lot of progress in a hurry. If they are loaded down with many, they stagger around, have a lot more trouble, and can’t get as far. And when they experience the mental equivalent of many packages dumped on them at once, they are squashed flat and can’t learn anything.  

So anything the teacher can do to reduce that cognitive load while presenting the material will help. Some ways to do so are obvious, such as slowing down. Others include having a clear, logical, explicit organization to the class (including making connections between different ideas presented and connections to things the students already know), using figures where appropriate rather than relying only on verbal descriptions and minimizing the use of technical jargon. All these things reduce unnecessary cognitive demands and result in more learning.

It should be "illegal" to write this proposal review

Like everywhere the success rate for research proposals in Denmark is around 10%.  This leaves review panels with the unenviable task of rejecting some proposals simply because there is not enough money, and not because the proposal is deficient in any meaningful way.  This happened to me a lot last year.  One of the proposals I re-submitted got the following review last year:

Your application was found very worthy of support.  This means that your professional qualifications, your CV, and your project was of such quality and character that it would have been funded had there been sufficient funds.

This year, the very same proposal was rejected with the following justification (emphasis, mine original at the end of the post.)

Reasons for denial:
Independent Research Council | Natural Sciences in its treatment of your application emphasized the importance of the evaluation criteria defined in the notice you were looking for in relation to, and weighted your application against the other applications that your application was in competition with. In comparison with the applications receiving funding, found strands that your application does not have quite the same degree: 

• demonstrate that your scientific production within the project area is on the same very high level. It appears from your CV that your publications within the project's subject area are not, to the same extent, published in the most respected journals.

The difference in CVs was four new publications, all in PLoS ONE. Did I not get funded because I published in PLoS ONE?  Well, probably not, since I didn't get funded the first time either.  I think they merely grasping at any old straw when de-selecting the last 20-30% of proposals. Never-the-less it is a completely non-sensical justification unworthy of anyone who call themselves scientists, and should be "against the law", i.e. against council policy, much like it now is in the UK:

When assessing proposals for research funding RCUK considers that it is the quality of the research proposed, and not where an author has or is intending to publish, that is of paramount importance.

Anyway, glad I got that off my chest.  Now on to bigger and better things.
-----
Original Danish text

Begrundelse for afslaget:
Det Frie Forskningsråd | Natur og Univers har i sin behandling af din ansøgning lagt vægt på de vurderingskriterier, der fremgik af det opslag, du søgte i forhold til, og vægtet din ansøgning mod de øvrige ansøgninger, som din ansøgning var i konkurrence med. I sammenligning med de ansøgninger, der fik bevilling, fandt rådet, at din ansøgning ikke i helt samme grad: 

• dokumenterer, at din videnskabelige produktion inden for projektets område er på samme meget høje niveau. Det fremgår af dit CV, at dine publikationer inden for projektets fagområde ikke i helt samme omfang er publiceret i de allermest anerkendte tidsskrifter.

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Paying for PeerJ articles ... is easy

The PeerJ pricing scheme can seem a little confusing at first but it is actually pretty easy to use in my experience.

We recently submitted a paper, which is now accepted!, and we have just submitted a new paper. I am the corresponding author on both and pay for all the authors.

When we submitted the first paper I simply made a free account on PeerJ and submitted the paper. When the reviews came back I decided that it was very likely that they would accept the paper so I paid $99 for a basic membership for all the authors (Martin, Luca, Casper, and myself).

We have now submitted a second paper.  Martin, Luca and myself are co-authors together with Julie, Christian, Werner and Allan - but Casper is not a co-author this time.  Below is a screenshot of one of the pages I see on my PeerJ account when I log in (it also contains email addresses, which I have censored).

As you can see PeerJ makes it very easy for me to see how much I have to pay for each co-author. To pay, I simply check the appropriate action boxes and click an "upgrade now" button further down the page.  Of course, I'll wait for the reviews before making a decision.

I assume the web-page will also keep track of the date of the last submission by a particular co-author so that, for example, Casper can publish another article for free next year without needing to upgrade.

This work is licensed under a Creative Commons Attribution 3.0 Unported License.