[gmx-users] pretty large coulomb contribution to free energy

[Ahmet Yıldırım]

Dear users,

The free energy of decoupling the ligand from the complex I get is about
457 kcal/mol. If for ligand in solution I get -5 kcal/mol, and for the
restraints -8 kcal/mol. Binding free energy is 457-5-8=444 kcal/mol. A
value over 400-500 kcal/mol is not unexpected for decoupling the ligand
from the complex? Anyone experienced similar problem? The problem is the
intramolecular interaction of the ligand? How about this Gromacs version
https://github.com/gromacs/gromacs/tree/022ad08b2fd0c1de085e88ac81a61841c4daea9c
?

Ligand I used is neutral. Gromacs version is 4.6.5

Free energy control parts of my input files are below.

############ For decoupling the ligand from the complex #########
; Free energy control stuff
init-lambda-state        = 5
free_energy              = yes
sc-alpha                 = 0.5
sc-power                 = 1.0
sc-sigma                 = 0.3
restraint-lambdas        = 0.0 0.01 0.025 0.05 0.075 0.1 0.2 0.35 0.5 0.75
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0
1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
coul-lambdas             = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0
1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas              = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00
0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6
0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0
nstdhdl                  = 10

pull           = umbrella
pull_geometry  = distance
pull_dim       = Y Y Y
pull_start     = no
pull_init1     = 0.2980769

pull_ngroups   = 1
pull_group0    = atom-p
pull_group1    = atom-l
pull_k1        = 0.0   ; kJ*mol^(-1)*nm^(-2)
pull_kB1       = 4184  ; kJ*mol^(-1)*nm^(-2)


######## For solvation free energy ###########
; Free energy control stuff
init-lambda-state        = 5
free_energy              = yes
sc-alpha                 = 0.5
sc-power                 = 1.0
sc-sigma                 = 0.3
coul-lambdas             = 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.00
1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas              = 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.05
0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0
nstdhdl                  = 10
couple-intramol          = yes
couple-moltype           = MOL
couple-lambda0           = vdw-q
couple-lambda1           = none



-- 
Ahmet Yıldırım