# Solvation free energy calculation of organic molecule in binary mixtures and convergence
**URL:** https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403
**Category:** User discussions
**Tags:** analysis-tools
**Created:** [January 29, 2025, 9:34am UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403 "2025-01-29T09:34:52Z")
**Posts on this page:** 4
**Page:** 1
### Author:  [@mjm91](https://gromacs.bioexcel.eu/u/mjm91)
#### Post date: [January 29, 2025, 9:34am UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403/1 "2025-01-29T09:34:52Z")
Dear all,
I am trying to calculate the solvation free energy for an organic molecule (merocyanine) in pure water and water/acetonitrile binary mixture.
I decoupled the charged coulomb interactions by making the charges 0 in the [atoms] directive for the organic molecule. Then I ran energy minimization, equilibration (200 ps) and production run for 1 ns. I have varied the Lambda-vdw values :
free\_energy = yes
init\_lambda\_state = 0
delta\_lambda = 0
calc\_lambda\_neighbors = 1 ; only immediate neighboring windows
couple-moltype = Merocyanine ; name of moleculetype to decouple
couple-lambda0 = vdw ; only van der Waals interactions
couple-lambda1 = none ; turn off everything, in this case only vdW
couple-intramol = no
; 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
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
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
; Options for the decoupling
sc-alpha = 0.5
sc-coul = no ; linear interpolation of Coulomb (none in this case)
sc-power = 1
sc-sigma = 0.3
nstdhdl = 10
After choosing 21 Lambda values and running minimization, equilibration and production MD for all these Lambda values, I used gmx bar to calculate the solvation free energy. The delta G value for decoupling the organic molecule obtained from the above simulations is: -0.10 +/- 0.68 kJ/mol.
Is this value acceptable or it is erroreneous as the error bar is higher than the value itself. Also, how do I check if the free energy calculation is converged or do I need more Lambda values or do I need to run the simulations for longer time?
Any help would be appreciated, thank you
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### Author:  [@hess](https://gromacs.bioexcel.eu/u/hess)
#### Post date: [January 29, 2025, 10:40am UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403/2 "2025-01-29T10:40:30Z")
It looks like you need to read up on basic physics. You need to decide what accuracy you want. I would consider 0.7 kJ/mol a high accuracy in this context. You don’t write how long you simulated, but an error of 0.7 kJ/mol seems very small for such a large molecule.
Why did you manual zero the charges in the topology file? The couple option already zeros those for you.
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### Author:  [@mjm91](https://gromacs.bioexcel.eu/u/mjm91)
#### Post date: [January 29, 2025, 2:50pm UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403/3 "2025-01-29T14:50:38Z")
Thank you for your reply. I was wondering that the free energy value is 0.1 kJ/mol whereas the error is six times larger than the free energy value and I was hoping if that is fine. Regarding the coulomb interactions, I was trying to follow a tutorial where the charges for the molecule is kept zero in the topology file and the mdp settings were provided accordingly. I might have to read more on the setting the mdp options.
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### Author:  [@mjm91](https://gromacs.bioexcel.eu/u/mjm91)
#### Post date: [January 29, 2025, 2:51pm UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation-of-organic-molecule-in-binary-mixtures-and-convergence/11403/4 "2025-01-29T14:51:26Z")
I have run the equilibrium simulations for 200 ps and production MD for 1 ns for a little over 3000 atoms in the system for each lambda values.