GROMACS version: 2018.3

Hello!

While I was testing the solubility of some small organic molecules under charmm36, I found out the simulated solubility is far off from the experimental value.

For example, the documented solubility of benzene is ~20 mmol/L. However, in my simulations, none of the benzene molecules aggregate at 200 mmol/L. The same happened with heptane. Although phase separation happens with enough organic molecules.

What is the possible explanation?

Attached is the md run mdp file.

Thank you!!

define =

;refcoord_scaling =

; RUN CONTROL PARAMETERS

integrator = md

; Start time and timestep in ps

tinit = 0

dt = 0.0025

nsteps = 40000000

; For exact run continuation or redoing part of a run

init_step = 0

; Part index is updated automatically on checkpointing (keeps files separate)

simulation_part = 1

; mode for center of mass motion removal

comm-mode = linear

; number of steps for center of mass motion removal

nstcomm = 1

; group(s) for center of mass motion removal

comm-grps =

; OUTPUT CONTROL OPTIONS

; Output frequency for coords (x), velocities (v) and forces (f)

nstxout = 50000

nstvout = 50000

nstfout = 50000

; Output frequency for energies to log file and energy file

nstlog = 10000

nstcalcenergy = 1000

nstenergy = 10000

; Output frequency and precision for .xtc file

nstxout-compressed = 5000

compressed-x-precision = 1000

; This selects the subset of atoms for the compressed

; trajectory file. You can select multiple groups. By

; default, all atoms will be written.

compressed-x-grps =

; Selection of energy groups

;energygrps = MCH PFA Water Ion

; NEIGHBORSEARCHING PARAMETERS

; cut-off scheme (Verlet: particle based cut-offs, group: using charge groups)

cutoff-scheme = Verlet

; nblist update frequency

nstlist = 20

; ns algorithm (simple or grid)

ns_type = grid

; Periodic boundary conditions: xyz, no, xy

pbc = xyz

periodic_molecules = yes

; Allowed energy error due to the Verlet buffer in kJ/mol/ps per atom,

; a value of -1 means: use rlist

verlet-buffer-tolerance = 0.005

; nblist cut-off

rlist = 1.2

; OPTIONS FOR ELECTROSTATICS AND VDW

; Method for doing electrostatics

coulombtype = PME

coulomb-modifier = Potential-shift-Verlet

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 = cut-off

vdw-modifier = Potential-switch

; cut-off lengths

rvdw-switch = 1.0

rvdw = 1.2

; Apply long range dispersion corrections for Energy and Pressure

DispCorr = no

; Extension of the potential lookup tables beyond the cut-off

table-extension = 1

; Separate tables between energy group pairs

energygrp-table =

; Spacing for the PME/PPPM FFT grid

fourierspacing = 0.12

; FFT grid size, when a value is 0 fourierspacing will be used

fourier_nx = 0

fourier_ny = 0

fourier_nz = 0

; EWALD/PME/PPPM parameters

pme_order = 4

ewald_rtol = 1e-05

ewald-rtol-lj = 0.001

lj-pme-comb-rule = Geometric

ewald_geometry = 3d

epsilon_surface = 0

; OPTIONS FOR WEAK COUPLING ALGORITHMS

; Temperature coupling

Tcoupl = Nose-Hoover

; Groups to couple separately

tc-grps = water non-water

; Time constant (ps) and reference temperature (K)

tau_t = 1.0 1.0

ref_t = 300 300

; Pressure coupling

Pcoupl = Parrinello-Rahman

Pcoupltype = isotropic

; Time constant (ps), compressibility (1/bar) and reference P (bar)

tau_p = 4.0

compressibility = 4.5e-5

ref-p = 1.0

; GENERATE VELOCITIES FOR STARTUP RUN

gen_vel = yes

gen_temp = 298

gen_seed = -1

; OPTIONS FOR BONDS

constraints = all-bonds

; Type of constraint algorithm

constraint-algorithm = Lincs

; Do not constrain the start configuration

continuation = no

; Use successive overrelaxation to reduce the number of shake iterations

Shake-SOR = no

; Relative tolerance of shake

shake-tol = 1e-04

; Highest order in the expansion of the constraint coupling matrix

lincs-order = 4

; Number of iterations in the final step of LINCS. 1 is fine for

; normal simulations, but use 2 to conserve energy in NVE runs.

; For energy minimization with constraints it should be 4 to 8.

lincs-iter = 1

; Lincs will write a warning to the stderr if in one step a bond

; rotates over more degrees than

lincs-warnangle = 30

; Convert harmonic bonds to morse potentials

morse = no