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

Sebastien Cote sebastien.cote.4 at umontreal.ca
Wed Aug 15 20:23:37 CEST 2012

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 (?). 


> 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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