[gmx-users] E. coli's Inner Membrane Lipid Selection

Thomas Piggot t.piggot at soton.ac.uk
Sun Feb 19 02:02:54 CET 2017

That seems like a sensible thing to do given what you are wanting to 
look at (and is what I would probably do too in your situation).

I imagine what will be of far more importance than the membrane in your 
simulations, will be how you derive the parameters for the minocycline 
ligand and if they are good enough (although I can vaguely remember some 
decent looking CHARMM tetracycline parameters being published in the 
past, unless my memory completely deceives me).

Good luck


On 19/02/17 00:33, Jonathan Saboury wrote:
> Thank you for so much great information! Coming from a organic synthesis
> background (knowing little to no biology) this gave me a lot of useful
> information.
> I'm looking to simulate 2DRD (AcrB cocomplexed with Minocycline) and study
> the interaction of the complex. Here is a picture of the complex:
> http://i66.tinypic.com/rwovwp.jpg (Minocycline is in the top half of the
> protein in CPK, the bilayer is the bottom half of the protein.)
> I think I'll start with 3:1 POPE:POPG, since the interaction I'm studying
> is pretty far away from the membrane, and the presence of the bilayer is
> probably just to stabilize the protein. If that fails I'll go to a more
> complex membrane.
> Thanks again for your time and help!
> - Jonathan
> On Sat, Feb 18, 2017 at 2:34 PM, Thomas Piggot <t.piggot at soton.ac.uk> wrote:
>> Hi,
>> For 1), perhaps but it depends upon what you are doing and what you are
>> wanting to look at. Force field choice is (IMHO) likely to be more
>> important (and CHARMM36 should be a good choice as long as you get all your
>> mdp settings, etc., correct).
>> For 2), the composition looks fairly reasonable bar a couple of points.
>> I'm not aware of PS normally being a lipid found in E. coli, so I wouldn't
>> have this. I'm not completely positive what the Y tail is in your/the
>> CHARMM-GUI acronym (I think it is probably palmitoleoyl) but I believe
>> cardiolipin should have a similar tail composition to PG, as in E. coli
>> cardiolipin is synthesised directly from a combination of two PG's (unlike
>> in mitochondria, where it is made de novo IIRC). So something more like
>> PYPY for the four cardiolipin tails would likely give a better
>> representation of the real system. To be honest, how complex you go with
>> the membrane will likely depend upon what you want to do. A simple 75%
>> POPE, 25% POPG is a fairly accurate representation of the membrane. I know
>> there isn't a huge amount of oleoyl (18:1 delta9) tails in all the
>> available E. coli experimental data, but oleoyl is a nice mix of the two
>> most commonly found sn-2 chains: palmitoleoyl (16:1 delta 9) and
>> cis-vaccenyl (18:1 delta 11). That said, if you want as accurate as
>> possible, you can have all sorts of different types of lipid in there, with
>> different tail types. At some stages in the cell cycle there are high
>> amounts of cyclic rings in the tails instead of double-bonds, for example.
>> Plus the ratio of PG:cardiolipin changes during the cell cycle too, as
>> cardiolipin is synthesised and broken down (IIRC). Does, this matter? Would
>> this impact upon your simulations (as per your question 1)? These really
>> are questions for you to address. In my view, probably not a huge amount,
>> but you can't really tell for sure in your case without extensive testing
>> (e.g lots of different repeat simulations in each type of membrane, long
>> enough to ensure convergence and a statistical comparison of the results
>> you get for what you consider to be important properties that you want to
>> compare). A lot of work, that probably isn't worth it.
>> So, I guess my answer for both of these, is that it really depends upon
>> what you are wanting to study. For 1), it is hard to tell without extensive
>> testing for your example. For 2), how complex you go with your composition
>> is also up to you and what you are wanting to look at. At the one extreme,
>> a simple PC membrane could well be good enough, for example, if the protein
>> has been shown to experimentally behave fine in this type of membrane. If
>> you're not really sure, I would personally probably go with the simple 3:1
>> POPE:POPG mixture as a simple yet reasonable representation of the
>> membrane. One step further up in terms of complexity would be to include
>> cardiolipin and have some more realistic tails (1-palmitoyl 2-palmitoleoly
>> and 1-palmitoyl 2-cis-vaccenyl plus perhaps some cyclic ringed tails in
>> there too depending if there is a certain point in the cell-cycle you are
>> wanting to study).
>> Cheers
>> Tom
>> On 18/02/17 21:12, Jonathan Saboury wrote:
>>> Hello all,
>>> I'm trying to perform MD on a membrane protein AcrB. I am using charmm-gui
>>> to build the membrane but having difficulty deciding on membrane
>>> constituents.
>>> AcrB is a protein in E. coli's inner membrane:
>>> http://www.nature.com/nature/
>>> journal/v419/n6907/images/nature01050-f5.2.jpg
>>> Based on the below literature, I have chosen the following membrane: PYPE
>>> 70%, PYPG 14%, DPPS 8%, TYCL2 8%.
>>> Characterization of the Escherichia coli membrane structure and function
>>> during fedbatch cultivation: https://www.ncbi.nlm.nih.gov/
>>> pmc/articles/PMC514524/pdf/1475-2859-3-9.pdf
>>> My two main questions are:
>>> 1.) Does lipid choice affect MD simulation much? I'm using charmm36
>>> 2.) Does my lipid selection make sense? If not, why and what would you
>>> use?
>>> Thank you for your time!! :-)
>> --
>> Dr Thomas Piggot
>> Visiting Fellow
>> University of Southampton, UK.
>> --
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Dr Thomas Piggot
Visiting Fellow
University of Southampton, UK.

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