This blog has been started to make improvements on the manuscript titled "Response of the hydrophilic part of lipid membranes to changing conditions — a critical comparison of simulations to experiments", written by O. H. Samuli Ollila, and openly available at http://arxiv.org/abs/1309.2131.
Here is the abstract of the manuscript: "We compare the order parameters predicted for the hydrocarbon segments in lipid bilayer headgroup region by the Berger molecular dynamics simulation model to those measured by Nuclear Magnetic Resonance (NMR) experiments. We first show results for a fully hydrated POPC bilayer, and then focus on changes of the order parameters as a function of hydration level, NaCl and CaCl2 concentrations, and cholesterol content. The experimental headgroup order parameters are never reproduced. This indicates that under all of these conditions the used model is unable to correctly reproduce the headgroup structure. Consequently, many of the conclusions drawn over the years from this model might be erroneous."
Although I think that the manuscript is a high quality scientific document, it has not been submitted to any journal, instead its contents are discussed here. The reasons for this decision you can find in the post Why not submit to a journal?
The ultimate goal of this blog is to find an atomistic (preferably united-atom) force field that reproduces the experimental properties discussed in the manuscript. Naturally the optimal situation would be that some of the already available force fields would fulfill this goal. If this, however, turns out not to be the case, the goal will be to find the appropriate modifications.
All the work will be progressed openly in this blog, and anyone is free to join in. In the end of the project the manuscript, updated with the improvements made via this blog, will be submitted to an appropriate scientific journal. Authorship will be shared among the blog contributors, as described in the post On credits.
My current ideas about things to be done in order to achieve the goal are described below. Some of these issues are straighforward to do, especially for the people who already have done something similar. For example, if you have done CHARMM simulations on a lipid bilayer with ions it is relatively easy to calculate headgroup order parameters and share the results through this blog. Some of the issues are not that straighforward. Below I have listed some tasks which would improve the manuscripts significantly. In addition of these issues, any other comments, questions and contributions are very welcome.
Things to do:
- The CHARMM [Klauda et al. JPCB 114, 7830 (2010)] and the GAFF [Dickson et al. Soft Matter 8, 9617 (2012)] force fields give better order parameters for the headgroup under full hydration. Interesting question now is, would these force fields also reproduce the correct changes in the order parameters as a function of dehydration, ion cholesterol concentration? At least for Sodium [Valley et al. J. Membrane Biol. 244, 35 (2011)] and cholesterol [Lim et al. JPCB 116, 203 (2012)] simulations have already been done with the recent CHARMM model. The calculations of headgroup and glycerol order parameters from these simulations would be very informative.
- For the all-atom Stockholm lipids force field [Jämbeck et al. JPCB 116, 3164 (2012)] I have not seen order parameters calculated for headgroup or glycerol. These would be interesting to see.
- I have not seen the headgroup and glycerol order parameters for the united atom lipid force fields based on GROMOS by Kukol [JCTC 5, 615 (2009)] and by Chiu et al. [JPCB 113, 2748–2763 (2009)]. Poger et al. [J Comput Chem 31: 1117–1125, (2010)] comment the order parameters briefly, but more information would be interesting. Fore more details and discussion see the post on Some points concerning the POPC full-hydration results.
- If it turns out that none of the existing united-atom force fields can reproduce the experimental order parameters under the studied conditions, we should find the way to fix the models. This is probably not a straightforward task. I have presented some of my ideas and opinions in the post on Some points concerning the POPC full-hydration results.
- The ion parameters play naturally a large role in the interaction between ions and lipids, making this a particularly complicated issue. I have written some ideas in the post on Some points concerning the ion-membrane interaction results.
All the files which are used to run the simulations and analysis for the manuscript can be downloaded from: http://dx.doi.org/10.6084/m9.figshare.790722
Everyone is invited to discuss, criticize and contribute to the manuscript through this blog. Communication and contributions can be done by writing the comments to the blog posts. If you pick one of the already determined tasks, it might be good to inform readers to avoid overlapping contributions.