[gmx-users] FW: Free energy of solvation using the Bar method

[Innocenti Malini, Riccardo]

Dear all,

I am currently trying to calculate the free energy of solvation for a small hydrophobic molecule in water using the OPLSaa force field, however for vdw lambda values above 0.2 my system continuously explodes.

Before starting the free energy calculations I equilibrated the system (100 ps in NVT and 4 ns in NPT ensemble). Then before starting the free energy calculations before each lambda point I minimized the energy using first the steepest descent method and then L-BFGS. The system is then simulated in the NVT ensemble where it tends to blows when the vdw for Lambda = 0.3. Below this value the system works fine in simulations of up to 8 ns and the system appears to be equilibrated.

I am not sure why this is happening. Would anybody have any advice? Here is the free energy section of the mdp file:

free_energy              = yes
couple-moltype           = Other
couple-lambda0           = vdw-q
couple-lambda1           = none
couple-intramol          = no
init-lambda              = -1
init_lambda_state        = 3
delta_lambda             = 0
nstdhdl                  = 10
fep-lambdas              =
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
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
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
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
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
calc_lambda_neighbors    = 1
init-lambda-weights      =
dhdl-print-energy        = no
sc-alpha                 = 0.5
sc-power                 = 1
sc-r-power               = 6
sc-sigma                 = 0.3
sc-coul                  = no
separate-dhdl-file       = yes
dhdl-derivatives         = yes
dh_hist_size             = 0
dh_hist_spacing          = 0.1

Thank you in advance for your help.

Kind regards,
Riccardo