Membrane Equilibrium

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1

GROMACS version: 2021.4
GROMACS modification: Yes/No
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Hello,

Before proceeding to the production run, I was performing membrane equilibration. Since I expected the deprotonated lipid to migrate toward the membrane core, I planned to monitor box size changes as an indicator of system stabilization. I’ve previously had success using this method for equilibration.

Below is the .mdp file I used:

title		= KALP15-DPPC Production MD 
; Run parameters
integrator	= md
nsteps		= 50000000
dt		= 0.002
; Output control
nstxout		= 0
nstvout		= 0
nstxtcout	= 30000
nstenergy	= 30000
nstlog		= 30000
; Bond parameters
continuation	= yes
constraint_algorithm = lincs
constraints	= h-bonds
lincs_iter	= 1
lincs_order	= 4
; Neighborsearching
ns_type		= grid
nstlist		= 5
rlist		= 1.2
rcoulomb	= 1.2
rvdw		= 1.2
; Electrostatics
coulombtype	= PME
pme_order	= 4
fourierspacing	= 0.16
; Temperature coupling
tcoupl		= v-rescale
tc-grps		= SOL_ION MEMB
tau_t		= 0.5 0.5
ref_t		= 300 300
; Pressure coupling
pcoupl		= parrinello-rahman
pcoupltype	= semiisotropic
tau_p		= 12.0
ref_p		= 1.0 1.0
compressibility = 3.0e-5 3.0e-5
; PBC and dispersion correction
pbc		    = xyz
DispCorr	= EnerPres
; Velocity generation
gen_vel		= no
; Center of mass motion removal
nstcomm         = 1
comm-mode       = Linear
comm-grps       = SOL_ION MEMB
refcoord_scaling = com

At 300 K, the membrane appeared as follows (attached image).

image
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At 300 K, the membrane appeared to be stable and there was no noticeable change in box size or lipid distribution. However, to accelerate equilibration, I increased the temperature to 373 K. Upon doing so, I observed a drastic shrinkage of the box size and elongation of the membrane in the Z-direction, as shown in the image below.

image
image1060×750 162 KB

image
image1060×750 98.9 KB

I’m wondering whether this is an expected effect of the elevated temperature or if there might be something incorrectly set in my .mdp file. If this issue is due to the temperature increase, would it be more appropriate to simply extend the equilibration time at 300 K instead?

Thank you in advance for your insights!

2

Hi,

which lipid composition for your membrane do you use, and how long are your simulations?

Best,
Marius

3

The composition is identical to that of Pfizer’s(BNT162b2) formulation.
A simulation was conducted at 373 K for approximately 200 ns, during which the membrane underwent the following morphological changes.

4

Was the membrane self-assembled? And what is the lateral size of the membrane at the start of the simulation? I would guess that the migration of the aminolipids into the membrane core lead to a strong shrinkage of the membrane surface area, and at a certain point periodic boundary artefacts come into play. In this paper the authors circumvented this issues by increasing the membrane size.