[gmx-users] CHARMM36 - Smaller Area per lipid for POPE - Why?

[Felipe Pineda, PhD]

Hi Sébastian,

I think the "magic word" in this issue would be surface tension and the 
proper ensemble for the simulation NPgammaT. This is very well discussed 
in the paper I advised to you a couple of days ago. The issue is by no 
means trivial, although I'm not an expert to judge it. You can find an 
imho very well-founded theoretical discussion in, e.g., Lindahl, E. and 
Edholm, O. Spatial and energetic-entropic decomposition of surface 
tension in lipid bilayers from molecular dynamics simulations. J. Chem. 
Phys.(2000)113, 3882.

Good luck!

Felipe

On 08/15/2012 08:23 PM, Sebastien Cote wrote:
> Thanks for the advices Chris.
>
> My peptide is known to be more favorably to PE than PC membrane that is why I am using POPE.
>
> Experimentally, the liquid phase transition is at 298K for POPE (if I am not mistaken). Is your 323K refer to some simulations?
>
> At first I wanted to use the new CHARMM36 lipids parameters because they are supposed to solve the previous CHARMM27 issue with the area per lipid. However, I am consistently obtained smaller APL then experiment and I am not able to reproduce the published APL obtained for POPE, even if I am starting from their equilibrated 80-POPE membrane and use same simulation conditions. That was the reason for starting this thread on the mailing list.
>
> Unfortunately, my peptide conformational space in solution is only well-represented by CHARMM27 (equivalently in CHARMM36), so I can not use Berger's lipid parameters with OPLS or GROMOS even if it would be preferable as they do not have APL inconsistency and are united-atom.
>
> I will made some tests in the NPAT ensemble. Perhaps the NPAT effects can be made neglegible by using bigger membrane compared to my peptide's size (?).
>
> Sebastien
>
> ----------------------------------------
>> From: chris.neale at mail.utoronto.ca
>> To: gmx-users at gromacs.org
>> Date: Wed, 15 Aug 2012 17:29:29 +0000
>> Subject: [gmx-users] CHARMM36 - Smaller Area per lipid for POPE - Why?
>>
>> The area per lipid (APL) will certainly affect the free energy of peptide/protein binding to a lipid bilayer.
>> I have not used charmm lipids extensively, but from what I understand they older charmm lipids required
>> NPAT to get the correct APL. The newer charmm lipids were supposed to solve that problem, but I have heard
>> it said that, though the problem has been alleviated to some extend, it still remains.
>>
>> If I were you, I'd use POPC in place of POPE. POPE is notorious for giving too-small APL's in simulations and I think
>> it even requires temperatures of 323 K to enter the liquid phase.
>>
>> That said, I don't have a specific answer to your question of whether there are other affects of NPAT vs. NPT.
>> It is plausible that NPAT-based fluctuations could affect the pathway or the kinetics.
>>
>> PS: I was not referring to lipid rafts, but the separate diffusion of the upper and lower leaflets. Once the peptide is
>> fully inserted, if it spans both leaflets, this will tend to reduce this leaflet-specific diffusion and would represent an
>> entropic penalty for binding (not sure how large).
>>
>> Chris.
>>
>>> Dear Peter,
>>>
>>> I also used h-bonds and I also switch LJ interaction from 0.8 nm to 1.2 nm (as in Klauda's paper). I will retry with a more solvated membrane.
>>>
>>> Would you have any thought on how the NPAT ensemble might affect peptide-membrane interactions like I am studying i.e. peptide is totally solvated, then adsorb, and finally may insert? The paper on peptide-membrane interaction like this usually use united-atom lipid in the NPT ensemble. Most of the work I have seen on Charmm membrane in the NPAT ensemble were for embedded membrane protein.
>> Sorry, but I only have experience with large pre-embedded membrane proteins,
>> and those are governed both by signal sequences and post-translational
>> modification.
>>
>> Chris's last email on the subject might lead to the hypothesis that lipid
>> raft translation as the leaflets "slide" past one another could be a
>> contributing factor to adsorbption of your species.
>>
>>> Thanks,
>>>
>>> Sebastien
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| Luis Felipe Pineda De Castro, PhD |
| Computational Chemist - Postdoc   |
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