[gmx-users] mdp file for slow-growth free energy calculation

[Matteo Busato]

Good morning to everyone,


I am trying to perform a very simple calculation of the free energy of hydration of a Zinc ion in a box of water, using the slow-growth method and the gmx_bar program with GROMACS 5.0.4. I've taken the LJ paramethers for Zn2+ from the Stote and Karplus article dated 1995 (sigma=0.195nm and epsilon=1.046KJ/mol), but I've obtained a DG of just 1500 KJ/mol more on less against the experimental value of more than 2000 KJ/mol. The fact is that the VdW contribute results just 2.92KJ/mol, and the Coulomb more or less 1500KJ/mol.

I can't figure out where the error is, but I think it can just be the .mdp file, so I'll post here the mpd I've used, for example for the dynamics. Both the method and the mdp are based on Dr. Justin Lemkul tutorial for the DG of methane in water, I've just added the Coulombs growth as recommended in the last page of the tutorial and then obtained 40 values of lambdas. This is the mdp I'm using (lambda=32):


; Run control
integrator               = sd       ; Langevin dynamics
tinit                    = 0
dt                       = 0.002
nsteps                   = 500000   ; 1 ns
nstcomm                  = 100
; Output control
nstxout                  = 500
nstvout                  = 500
nstfout                  = 0
nstlog                   = 500
nstenergy                = 500
nstxout-compressed       = 0
; Neighborsearching and short-range nonbonded interactions
cutoff-scheme            = verlet
nstlist                  = 20
ns_type                  = grid
pbc                      = xyz
rlist                    = 1.2
; Electrostatics
coulombtype              = PME
rcoulomb                 = 1.2
; van der Waals
vdwtype                  = cutoff
vdw-modifier             = potential-switch
rvdw-switch              = 1.0
rvdw                     = 1.2
; Apply long range dispersion corrections for Energy and Pressure
DispCorr                  = EnerPres
; Spacing for the PME/PPPM FFT grid
fourierspacing           = 0.12
; EWALD/PME/PPPM parameters
pme_order                = 6
ewald_rtol               = 1e-06
epsilon_surface          = 0
; Temperature coupling
; tcoupl is implicitly handled by the sd integrator
tc_grps                  = system
tau_t                    = 1.0
ref_t                    = 300
; Pressure coupling is on for NPT
Pcoupl                   = Parrinello-Rahman
tau_p                    = 1.0
compressibility          = 4.5e-05
ref_p                    = 1.0
; Free energy control stuff
free_energy              = yes
init_lambda_state        = 32
delta_lambda             = 0
calc_lambda_neighbors    = 1        ; only immediate neighboring windows
; Vectors of lambda specified here
; Each combination is an index that is retrieved from init_lambda_state for each simulation
; init_lambda_state        0    1    2    3    4    5    6    7    8    9    10   11   12   13   14   15   16   17   18   19   20   21   22   23   24   25   26   27   28   29   29   30   31   32   33   34   35   36   37   38   39
vdw_lambdas              = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
coul_lambdas             = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
; We are not transforming any bonded or restrained interactions
bonded_lambdas           = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
restraint_lambdas        = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
; Masses are not changing (particle identities are the same at lambda = 0 and lambda = 1)
mass_lambdas             = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
; Not doing simulated temperting here
temperature_lambdas      = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
; Options for the decoupling
sc-alpha                 = 0.5
sc-coul                  = no       ; linear interpolation of Coulomb (none in this case)
sc-power                 = 1.0
sc-sigma                 = 0.3
couple-moltype           = ZN       ; name of moleculetype to decouple
couple-lambda0           = none     ; no interactions at lambda=0
couple-lambda1           = vdw-q    ; turn on both vdW and Coulomb
couple-intramol          = no
nstdhdl                  = 10
; Do not generate velocities
gen_vel                  = no
; options for bonds
constraints              = h-bonds  ; we only have C-H bonds here
; Type of constraint algorithm
constraint-algorithm     = lincs
; Constrain the starting configuration
; since we are continuing from NPT
continuation             = yes
; Highest order in the expansion of the constraint coupling matrix
lincs-order              = 12



Thank you in advance for your advice.


Matteo Busato