Hi,
in addition to Chris' comments, I think one good way for getting APL of
a lipid mixture is the one proposed by Edholm and Nagle :
http://www.cell.com/biophysj/abstract/S0006-3495%2805%2972827-7.
The idea is to run simulations at different concentrations of [A] and [B].
Ciao,
Patrick
Le 09/05/2013 01:06, Christopher Neale a écrit :
It is a really bad idea to use standard tip3p with charmm36 lipids (see the
Piggot paper that you referenced and also Sapay, N. et al. 2010 J. Comp. Chem.
32, 1400-1410 + probably others).
dt 0.001 with nstlist 5 seems like overkill on the nstlist update frequency
(not a problem though).
Here's how I do charmm36 lipid simulations:
constraints = all-bonds
lincs-iter = 1
lincs-order = 6
constraint_algorithm = lincs
integrator = sd
dt = 0.002
tinit = 0
nsteps = 5000000
nstcomm = 1
nstxout = 5000000
nstvout = 5000000
nstfout = 5000000
nstxtcout = 50000
nstenergy = 50000
nstlist = 10
nstlog=0 ; reduce log file size
ns_type = grid
vdwtype = switch
rlist = 1.2
rlistlong = 1.3
rvdw = 1.2
rvdw-switch = 0.8
rcoulomb = 1.2
coulombtype = PME
ewald-rtol = 1e-5
optimize_fft = yes
fourierspacing = 0.12
fourier_nx = 0
fourier_ny = 0
fourier_nz = 0
pme_order = 4
tc_grps = System
tau_t = 1.0
ld_seed = -1
ref_t = 310
gen_temp = 310
gen_vel = yes
unconstrained_start = no
gen_seed = -1
Pcoupl = berendsen
pcoupltype = semiisotropic
tau_p = 4 4
compressibility = 4.5e-5 4.5e-5
ref_p = 1.0 1.0
For a pure POPC bilayer with Charmm36 lipids and tips3p water, I get ~ 0.64
nm^2/lipid (not using grid-mat, just looking at box dimensions).
If I use regular tip3p instead, the APL decreases a lot and eventually forms a
gel. In simple terms of APL and phase, you can get the same results as tips3p
(0.64 nm^2/lipid) if you use tip4p (and spce is not too bad, but is still not
as close as tip4p). Note tip4p will run faster than tips3p by a large margin.
Nevertheless, I use tip3sp in all of my work with charmm36.
Also, note that ions can shrink your APL, particularly Na+ (and divalent
cations are even worse). My simulations use 50 mM KCl, which basically doesn't
affect the average APL (although 50 mM NaCl does noticeably reduce the APL).
Finally, I am not convinced that a per-molecule area per lipid is a useful quantity to
compare to experimental areas per lipid. I haven't looked at Grid-Mat myself, but there
must be a lot of assumptions underlying any analysis that tried to assign an
"area" to a single 3D lipid. If I were you, I'd be looking for expt. results of
APL for POPC vs. POPE vs. 70%POPC/30%POPE. Also, are you entirely sure that you didn't
mix up the POPC vs. POPE values? It looks to me like a simple labelling error enough that
it warrants a second look.
Chris.
-- original message --
I've been experimenting with simulations of mixed bilayers (512 lipids in
total, 70% POPC, 30% POPE) using the charmm36 parameter set in gromacs, and
have a couple of questions. I know this has been discussed before, but I'd
appreciate some input nonetheless :-)
The relevant sections of my mdp-file are pasted below:
; Start time and timestep in ps
tinit = 0
dt = 0.001
nsteps = 100000000
; NEIGHBORSEARCHING PARAMETERS
; nblist update frequency
nstlist = 5
; ns algorithm (simple or grid)
ns_type = grid
; Periodic boundary conditions: xyz, no, xy
pbc = xyz
periodic_molecules = no
; nblist cut-off
rlist = 1.2
; long-range cut-off for switched potentials
rlistlong = 1.4
; OPTIONS FOR ELECTROSTATICS AND VDW
; Method for doing electrostatics
coulombtype = PME
rcoulomb-switch = 0
rcoulomb = 1.2
; Relative dielectric constant for the medium and the reaction field
epsilon_r = 1
epsilon_rf = 1
; Method for doing Van der Waals
vdw-type = switch
; cut-off lengths
rvdw-switch = 0.8
rvdw = 1.2
; Apply long range dispersion corrections for Energy and Pressure
DispCorr = No
; OPTIONS FOR WEAK COUPLING ALGORITHMS
; Temperature coupling
tcoupl = V-rescale
nsttcouple = -1
nh-chain-length = 10
; Groups to couple separately
tc-grps = System
; Time constant (ps) and reference temperature (K)
tau_t = 0.1
ref_t = 300
; Pressure coupling
pcoupl = Parrinello-Rahman
pcoupltype = semiisotropic
nstpcouple = -1
This is as far as I can tell from earlier discussions on the list, and also
from reading the Piggott et al. paper in JCTC, the correct settings for
charmm36.
After a simulation of ~50 ns, I use GridMatMD to calculate the area per
headgroup of POPC and POPE, respectively, and get what I think are not 100%
acceptable results (but maybe they are)
For POPC, I get 59,7 A^2, and for POPE, I get 63,1 A^2.
The value for POPE would have been fine I suppose if it hadn't been for the
fact that the APL for POPC is smaller. Should it not be larger than POPE?
I notice in the Piggott-paper that they in the supplement for some
simulations of POPC also get APL's of around 59-60 (without POPE of
course), and that the results depend to some extent also on the usage of
TIP3P vs TIP3SP water models. I have been using "normal" TIP3P here.
Could anyone comment on (a) my mdp-file settings, and (b) the resulting
APL, and tell me if I should be worried about anything?
THANKS
--
_______________________________________________________________
Patrick FUCHS
Dynamique des membranes et trafic intracellulaire
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot
Bâtiment Buffon, 15 rue Hélène Brion, 75013 Paris
!!! ATTENTION, nouveau numéro de téléphone !!!
Tel : +33 (0)1 57 27 80 05 - Fax : +33 (0)1 57 27 81 35
E-mail address: patrick.fu...@univ-paris-diderot.fr
Web Site: http://www.dsimb.inserm.fr/~fuchs
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