Solvation free energy for positive charged molecules

User discussions
1

GROMACS version: 2022.1
GROMACS modification: Yes/No
Here post your question:

I want to know the solvation free energy of my molecule (name it A), it is positively charged (+1).
I added one counterion (name it B) to the system and neutralized the system.

Now I am wondering in the .mdp file for solvation MD, how to set the “couple-moltype”?
Should it be “couple-moltype = A” or “couple-moltype = A+B” ?

If it is “couple-moltype = A”, how about the influence coming from the counterion in the system?
If it is “couple-moltype = A+B”, the solvation free energy calculated here also includes the solvation free energy of the counterion, how to remove this part and get the real solvation free energy of molecule A?

Anyone has suggestions on how to get the solvation free energy of charged molecules? Thank you!

2

If you want to use couple-moltype, you need to put the counterion in the same moleculetype definition as the molecule.

But it is impossible to get reasonable absolute solvation free energies for charged molecules. You need some reference free-energy for a reference charged molecule, which is usually a proton. But AFAIK, the uncertainty of this value is very large. In practice it only makes sense to determine free-energy differences between states with the same net charge.