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

[Christopher Neale]

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