Monday, July 20, 2015

Revision requested for the first manuscript

The Journal of Physical Chemistry has sent us the reviewer comments on the first manuscript written based on the work in this blog. Major revision is requested before potential publication, however, based on the comments I am quite optimistic for the acceptance. I have asked the editor, if we can make the reviewer comments publicly available, but am yet to receive a reply. In the meanwhile, I wrote preliminary answers to the reviewer comments (available on GitHub) and sent the reviewer comments to the authors of the publication. Other followers can try to guess the original reviewer comments from the replies, until we hopefully get a permission to make also the original comments available.

If you want to comment or modify the answers, you can comment this post or (preferably) modify  directly the answer on GitHub and make a pull request.

In addition to replying the comments, there are some other things to do before the submission of the revised version:
  • Make the table of content figure. I do not have any good idea for this and also I do not have much time right now, so any ideas and actions are welcome.
  • Clean the GitHub repo a bit and create a doi for it.


  1. Hi,

    I compute, as suggested, the angle between g2-g3 (and g1-g3) and the membrane normal for the simulations with Cholesterol (I have done it with my simulations, i.e 'HS' and the ones of Fernando, i.e 'F').

    Here the results:
    Simulation g1-g3 g2-g3
    0% HS 65.75 46.71
    0% F 65.27 46.63
    10% F 65.62 46.83
    15% F 64.43 46.68
    20% HS 66.16 46.45
    20% F 67.39 47.32
    25% F 66.13 46.77
    35% F 67.82 48.39
    50% HS 67.12 50.83
    50% F 66.98 50.56

    The differences are not really striking. I could also compute the standard error if needed.

    I agree with the comment 3, maybe we could explain a bit more the quantification. What are the range of values for "almost within experimental error", "clear deviation from experiments" and "major deviation from experiments"? and how the severity was computed.


    1. I have now added this data in the supplementary material, updated the text and the reply to the reviewer:

  2. I have now received the reply from the Journal of Physical Chemistry to the question if we can make the reviewer comments publicly available. The reply was that it is not allowed. The answers to the comments are available in the GitHub, thus the non-authors can try to guess the original comments from the replies.

  3. The deadline for the submission of the revised version is 22-Aug-2015.

    I think that the replies to the reviewer are pretty much finished now, except the point 3 which is discussed now here:

    Also I do not have the TOC figure yet, thus all ideas related to this are very welcomed.

    Once these two issues are managed we can submit the revision. Also other comments regarding the replies are welcomed before submission.

    1. I made a first try of TOCS: If someone wants to modify it, the ppt file is here: Let me know what you think.

    2. I think this looks very good! Thanks. I added the 13C NMR splitting into the figure and made some minor changes. See

      I did also added all the files to GitHub. If you want to modify but not to use GitHub, you can do as before. I will update with GitHub then.

    3. Another suggestion for the TOC graphic (I put it together quickly so I'm not 100% sure that it's scientifically correct):

    4. Thanks for the other one as well. I think both would be good. I have opened a voting:

      Please, let us know if you have a favorite.

  4. I think both are great but I'll go with the one suggested by Patrick and Samuli.

  5. I am posting the following on behalf (and with the permission) of Matej Kanduc, so it can be openly discussed. (This is an email from him to me today.)


    Hey Sir,

    Today we were talking about this statement in the MS: "This may have some influence on dehydration energetic calculations made using the Berger model. [144,146]"

    I would say, at least the citations at the end should be removed. I don't think it is appropriate at all. The message would remain the same, but we would not single out particular authors' work as suspect. I guess, at this stage this statement is merely a speculation, not a firm fact, since nobody has proved it.

    Because you guys have a better idea about these influences discussed in the paper, you can better estimate how strong this claim is, and whether it be reworded, if not even omitted at all...


    1. If we would have this sentence without references, it would seem weird for most readers who do not know that there exists such calculations.

      On the other hand, the dehydration energetics is very relevant topic which has been discussed for very long time without consensus. One of the controversies has been the role of changes in lipid headgroup energetics due to dehydration. This is the main reason why dehydration is studied in this manuscript.

      The two publications cited here address this topic by studying the energetics using Berger model for lipid headgroup. For example, in citation 146 it is written:
      "The schematic illustration in Fig. 2E highlights the lipid headgroup configurational reorganization at short separations, which minimizes the electrostatic energy. This reorganization, in turn, is accompanied by structural ordering and thus by a configurational entropy loss, as witnessed by the pronounced rdf peaks for n_w = 4, and can be considered the main origin for the entropic repulsion −TS_{dir} in Fig. 2B."

      Now we have showed in this manuscript that the configurational sampling in the Berger model is not correct. I would say that it is quite likely that this incorrect configurational sampling affects also to the configurational entropy loss due to dehydration, mentioned in Ref. 146. On the other hand, there is also a theoretical possibility that it does not. Due to this theoretical possibility the sentence is, indeed, speculation which is pointed out by using word "may". The wording is also chosen such that it invites other scientists (including the authors of the cited work) to test if there is an influence or not.

      In conclusion, I think that this sentence should be included here due to the high relevance of the dehydration energetics discussion. The citations should be used to connect the statement to the previous research. I think that this is appropriate scientific discussion.

      It should be also noted that this sentence has been in the manuscript for months now and the content and the submission of this manuscript has been accepted by all authors. Also, this topic has been one of the main focus areas during the whole project and the core message has been the same (with varying strength) all the time. Thus, there has been numerous possibilities to comment on this during the last two years. However, this issue was raised now only one day before the deadline of replying the reviewer comments, in a situation where the acceptance of manuscript is very likely.

      Based on these points, I will keep the sentence and references as they are, unless there are objections presented before noon (Finnish time) tomorrow.


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