[gmx-users] Martini Lo-phase seems gel-like

[David Ackerman]

Hello Everyone,

I have been using the Martini CG forcefield to simulate phase separation in
a bilayer containing DPPC/DUPC/Chol at a ratio of 1:1:.5. Though this does
phase separate at 295 K, when I use mdp files based on
http://md.chem.rug.nl/cgmartini/images/parameters/exampleMDP/martini_v2.x_example.mdp,
the Lo phase has gel-like properties. Correlation functions between
cholesterols in the Lo phase persist for upwards of 10 nm, diffusion of Lo
lipids deep within the Lo phase (when corrected by subtracting the center
of mass motion of the bulk Lo phase) is on the order of 5E-10 cm^2/s.
Additionally, area per lipid are smaller and orders higher for Lo lipids
than would be expected.

Based on Waheed et al., Biophys. J, 103 (2012), it seems that the Lo-gel
transition temperature for a DPPC/Chol bilayer is ~ 300 K or more (when
cholesterol concentration is > 20%). However many Martini papers simulating
coexisting Lo/Ld patches with similar cholesterol concentrations do so at
295 K, as I have also tried. What I am finding however is that the Lo
phases I get at these temperatures is very gel-like. I have also seen the
aforementioned persistent correlations using the raft parameter files
provided at
http://md.chem.rug.nl/cgmartini/index.php/example-applications2/lipid-membranes
.

I am curious as to whether or not others have experienced these or similar
issues, or could provide any insights. I have copied an example mdp file
below.

Thank you,
David
______________________________________________________________

title                    = Martini

; TIMESTEP IN MARTINI
; Most simulations are numerically stable
; with dt=40 fs, some (especially rings and polarizable water) require
20-30 fs.
; Note that time steps of 40 fs and larger may create local heating or
; cooling in your system. Although the use of a heat bath will globally
; remove this effect, it is advised to check consistency of
; your results for somewhat smaller time steps in the range 20-30 fs.
; Time steps exceeding 40 fs should not be used; time steps smaller
; than 20 fs are also not required unless specifically stated in the itp
file.

integrator               = md
dt                       = 0.02
nsteps                   = 1250000000
nstcomm                  = 10
comm-grps                =

nstxout                  = 250000
nstvout                  = 250000
nstfout                  = 0
nstlog                   = 250000
nstenergy                = 250000
nstxtcout                = 0
xtc_precision            = 0
xtc-grps                 =
energygrps               = DPPC DUPC CHOL W

; NEIGHBOURLIST and MARTINI
; Due to the use of shifted potentials, the noise generated
; from particles leaving/entering the neighbour list is not so large,
; even when large time steps are being used. In practice, once every
; ten steps works fine with a neighborlist cutoff that is equal to the
; non-bonded cutoff (1.2 nm). However, to improve energy conservation
; or to avoid local heating/cooling, you may increase the update frequency
; and/or enlarge the neighbourlist cut-off (to 1.4 nm). The latter option
; is computationally less expensive and leads to improved energy
conservation

nstlist                  = 10
ns_type                  = grid
pbc                      = xyz
rlist                    = 1.2

; MARTINI and NONBONDED
; Standard cut-off schemes are used for the non-bonded interactions
; in the Martini model: LJ interactions are shifted to zero in the
; range 0.9-1.2 nm, and electrostatic interactions in the range 0.0-1.2 nm.
; The treatment of the non-bonded cut-offs is considered to be part of
; the force field parameterization, so we recommend not to touch these
; values as they will alter the overall balance of the force field.
; In principle you can include long range electrostatics through the use
; of PME, which could be more realistic in certain applications
; Please realize that electrostatic interactions in the Martini model are
; not considered to be very accurate to begin with, especially as the
; screening in the system is set to be uniform across the system with
; a screening constant of 15. When using PME, please make sure your
; system properties are still reasonable.
;
; With the polarizable water model, the relative electrostatic screening
; (epsilon_r) should have a value of 2.5, representative of a low-dielectric
; apolar solvent. The polarizable water itself will perform the explicit
screening
; in aqueous environment. In this case, the use of PME is more realistic.
;
; For use in combination with the Verlet-pairlist algorithm implemented
; in Gromacs 4.6 a straight cutoff in combination with the potential
; modifiers can be used. Although this will change the potential shape,
; preliminary results indicate that forcefield properties do not change a
lot
; when the LJ cutoff is reduced to 1.1 nm. Be sure to test the effects for
; your particular system. The advantage is a gain of speed of 50-100%.

coulombtype              = Shift  ;Reaction_field (for use with
Verlet-pairlist) ;PME (especially with polarizable water)
rcoulomb_switch          = 0.0
rcoulomb                 = 1.2
epsilon_r                = 15   ; 2.5 (with polarizable water)
vdw_type                 = Shift  ;cutoff (for use with Verlet-pairlist)
rvdw_switch              = 0.9
rvdw                     = 1.2  ;1.1 (for use with Verlet-pairlist)

;cutoff-scheme            = verlet
;coulomb-modifier         = Potential-shift
;vdw-modifier             = Potential-shift
;epsilon_rf               = 0   ; epsilon_rf = 0 really means epsilon_rf =
infinity
;verlet-buffer-drift      = 0.005

; MARTINI and TEMPERATURE/PRESSURE
; normal temperature and pressure coupling schemes can be used.
; It is recommended to couple individual groups in your system separately.
; Good temperature control can be achieved with the velocity rescale
(V-rescale)
; thermostat using a coupling constant of the order of 1 ps. Even better
; temperature control can be achieved by reducing the temperature coupling
; constant to 0.1 ps, although with such tight coupling (approaching
; the time step) one can no longer speak of a weak-coupling scheme.
; We therefore recommend a coupling time constant of at least 0.5 ps.
; The Berendsen thermostat is less suited since it does not give
; a well described thermodynamic ensemble.
;
; Pressure can be controlled with the Parrinello-Rahman barostat,
; with a coupling constant in the range 4-8 ps and typical compressibility
; in the order of 10-4 - 10-5 bar-1. Note that, for equilibration purposes,
; the Berendsen thermostat probably gives better results, as the Parrinello-
; Rahman is prone to oscillating behaviour. For bilayer systems the pressure
; coupling should be done semiisotropic.

tcoupl                   = v-rescale
tc-grps                  = DPPC DUPC CHOL W
tau_t                    = 1.0  1.0 1.0 1.0
ref_t                    = 295 295 295 295
Pcoupl                   = Berendsen
Pcoupltype               = semiisotropic
tau_p                    = 4.0 4.0  ;parrinello-rahman is more stable with
larger tau-p, DdJ, 20130422
compressibility          = 5e-5  5e-5
ref_p                    = 1.0  1.0

gen_vel                  = yes
gen_temp                 = 295
gen_seed                 = -1

; MARTINI and CONSTRAINTS
; for ring systems and stiff bonds constraints are defined
; which are best handled using Lincs.

constraints              = none
constraint_algorithm     = Lincs
unconstrained_start      = no
lincs_order              = 4
lincs_warnangle          = 30