Fwd: Irregular spontaneous membrane bending even in the absence of protein

From: Jie Shi (shijie0204_at_tamu.edu)
Date: Sun Sep 11 2022 - 10:36:09 CDT

Dear all,

I am attempting to run a simulation of a system containing both membrane
(POPC) and protein with NAMD 2.14 on HPC. However, I found the membrane
forms an irregular spontaneous bending. So I then tested it with a
membrane-only system (without the protein, so only the POPC bilayer, water,
and ions are included), and a similar bending is again shown up, which
suggests it’s not the protein that induces the bending in the membrane. The
snapshot showing the bending can be found here
https://urldefense.com/v3/__https://i.postimg.cc/hGJKG085/bending.png__;!!DZ3fjg!5TK-Tost5XQnSTwWQC2eFOZxPDxhKhmmmz9Py2_Cj9wc-lttu9PKsm2FqPpNA0omR5qXWvwXDAOZj19q0CvBX1E$ .

Then we move the membrane-only system to a local server and run the same
simulation. It is done with exactly the same input configuration files, and
the same input psf/pdb files. But on our local server, the bending never
happens.

Another weird thing we noticed: we then also started running several more
membrane simulations with/without protein, and all simulations show this
kind of bending in the membrane if run on HPC. And in all cases, the
bending happens along the Y-axis. This makes us wonder if it is a
systematic problem.

In summary, simulation on the local server: no irregular bending;
Simulation on HPC, bending appears very soon (within 10~ns) after the
harmonic restraints are removed ( those restraints are for the stages of
energy minimization and equilibrations).
We have never seen this issue before and we are wondering if it is related
to the version of NAMD and/or along with the HPC. Please let us know if
anyone else encounters a similar problem and if anyone knows how to solve
this issue. Thank you in advance!

More detailed information about our system:
a) Total atom numbers: 127146
b) There are 200 lipids (POPC) in each leaflet.
c) System dimensions:

cellBasisVector1 125.02 0.0 0.0
cellBasisVector2 0.0 127.08 0.0
cellBasisVector3 0.0 0.0 101.07
cellOrigin 0.0 0.0 0.0

More detailed information about our HPC:
1) It’s IBM Aimosx Cluster (NPL).
2) 20-core 2.5 GHz Intel Xeon CPUs
3) Each node has 8 NVIDIA Tesla V100 GPUs with 32 GiB HBM

More detailed information about our input files:
1) psf/pdb files are created by CHARMM GUI.
2) Input configuration file for the production run is also attached at the
end.
3) We also have tried using the input configuration files generated by
CHARMM GUI, it also leads to membrane bending if run on HPC.

Our research progress has been stuck for ~1 month due to this issue, please
help us resolve it. Any suggestions would be greatly appreciated. Thank you
again!

Best,
Jie

============================

#############################################################
## ADJUSTABLE PARAMETERS ##
#############################################################

structure step5_input.psf
coordinates step5_input.pdb
outputName popc_npt01

set temperature 303.15

# Continuing a job from the restart files
if {1} {
set inputname popc_eq5
binCoordinates $inputname.restart.coor
binVelocities $inputname.restart.vel ;# remove the "temperature"
entry if you use this!
extendedSystem $inputname.restart.xsc
}

firsttimestep 0

#############################################################
## SIMULATION PARAMETERS ##
#############################################################

# Input
paraTypeCharmm on

parameters toppar/par_all36m_prot.prm
parameters toppar/par_all36_na.prm
parameters toppar/par_all36_carb.prm
parameters toppar/par_all36_lipid.prm
parameters toppar/par_all36_cgenff.prm
parameters toppar/par_interface.prm
# parameters toppar/toppar_all36_moreions.str
parameters toppar/toppar_all36_nano_lig.str
parameters toppar/toppar_all36_nano_lig_patch.str
parameters toppar/toppar_all36_synthetic_polymer.str
parameters toppar/toppar_all36_synthetic_polymer_patch.str
parameters toppar/toppar_all36_polymer_solvent.str
parameters toppar/toppar_water_ions.str
parameters toppar/toppar_dum_noble_gases.str
parameters toppar/toppar_ions_won.str
parameters toppar/toppar_all36_prot_arg0.str
parameters toppar/toppar_all36_prot_c36m_d_aminoacids.str
parameters toppar/toppar_all36_prot_fluoro_alkanes.str
parameters toppar/toppar_all36_prot_heme.str
parameters toppar/toppar_all36_prot_na_combined.str
parameters toppar/toppar_all36_prot_retinol.str
parameters toppar/toppar_all36_prot_model.str
parameters toppar/toppar_all36_prot_modify_res.str
parameters toppar/toppar_all36_na_nad_ppi.str
parameters toppar/toppar_all36_na_rna_modified.str
parameters toppar/toppar_all36_lipid_sphingo.str
parameters toppar/toppar_all36_lipid_archaeal.str
parameters toppar/toppar_all36_lipid_bacterial.str
parameters toppar/toppar_all36_lipid_cardiolipin.str
parameters toppar/toppar_all36_lipid_cholesterol.str
parameters toppar/toppar_all36_lipid_dag.str
parameters toppar/toppar_all36_lipid_inositol.str
parameters toppar/toppar_all36_lipid_lnp.str
parameters toppar/toppar_all36_lipid_lps.str
parameters toppar/toppar_all36_lipid_mycobacterial.str
parameters toppar/toppar_all36_lipid_miscellaneous.str
parameters toppar/toppar_all36_lipid_model.str
parameters toppar/toppar_all36_lipid_prot.str
parameters toppar/toppar_all36_lipid_tag.str
parameters toppar/toppar_all36_lipid_yeast.str
parameters toppar/toppar_all36_lipid_hmmm.str
parameters toppar/toppar_all36_lipid_detergent.str
parameters toppar/toppar_all36_lipid_ether.str
parameters toppar/toppar_all36_carb_glycolipid.str
parameters toppar/toppar_all36_carb_glycopeptide.str
parameters toppar/toppar_all36_carb_imlab.str
parameters toppar/toppar_all36_label_spin.str
parameters toppar/toppar_all36_label_fluorophore.str

# NOTE: Do not set the initial velocity temperature if you
# have also specified a .vel restart file!
# temperature $temperature

# Periodic Boundary Conditions
# NOTE: Do not set the periodic cell basis if you have also
# specified an .xsc restart file!
if {0} {
cellBasisVector1 125.02 0.0 0.0
cellBasisVector2 0.0 127.08 0.0
cellBasisVector3 0.0 0.0 101.07
cellOrigin 0.0 0.0 0.0
}

wrapAll on

# Force-Field Parameters
exclude scaled1-4
1-4scaling 1.0
cutoff 12.0
switching on
vdwForceSwitching yes
switchdist 10.0
pairlistdist 16.0

# Integrator Parameters
timestep 2.0 ;# 2fs/step
rigidBonds all ;# needed for 2fs steps
nonbondedFreq 1
fullElectFrequency 2
stepspercycle 20

#PME (for full-system periodic electrostatics)
# values of 30, 32, 36, 40, 45, 48, 50, 54, 60, 64, 72, 75, 80, 81, 90, 96,
 100, 120, 128
if {1} {
PME yes
PMEInterpOrder 6; # interpolation order (spline order
6 in charmm)
PMEGridSpacing 1.0; # maximum PME grid space / used
to calculate grid size
}

# Constant Temperature Control
langevin on ;# do langevin dynamics
langevinDamping 1 ;# damping coefficient (gamma) of 5/ps
langevinTemp $temperature

# Constant Pressure Control (variable volume)
if {1} {
useGroupPressure yes ;# needed for 2fs steps
useFlexibleCell yes ;# no for water box, yes for membrane
useConstantRatio yes;

langevinPiston on
langevinPistonTarget 1.01325 ;# in bar -> 1 atm
langevinPistonPeriod 200.0
langevinPistonDecay 50.0
langevinPistonTemp $temperature
}

restartfreq 10000 ;# 1000steps = every 2ps
dcdfreq 10000 ;# 2 ps
xstFreq 10000 ;# every 20ps
dcdUnitCell yes;
outputEnergies 10000
outputTiming 10000
#outputPressure 500

# Fixed Atoms Constraint (set PDB beta-column to 1)
if {0} {
fixedAtoms on
fixedAtomsFile prot.fix
fixedAtomsCol B
fixedAtomsForces on
margin 3
}

#############################################################
## EXTRA PARAMETERS ##
#############################################################

# Put here any custom parameters that are specific to
# this job (e.g., SMD, TclForces, etc...)
if {0} {
constraints on
consexp 2
consref popc.eq.step5.pdb
conskfile popc.eq.step5.pdb
conskcol B
margin 3
}

#############################################################
## EXECUTION SCRIPT ##
#############################################################

# minimize 8000
run 10000000 ;# 20 ns (2fs timestep)

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