Ehsan,

In general the free energy of solvation (fes) can be considered as

Fes = free energy of solution - free energy of solvent - free energy of solute

The lower free energy means more stable. Thus, negative values in the first graph means instantaneous solvation. When you try to insert larger molecules in the solution, you try to cause more disturbance in the structur of the solvent molecules (imagine liquid water interactions including hydrogen bonds).

The pattern we have seen in one of our studies is the fes highly depends on the ratio of chaege/size of solvent, the bigger the ratio the more negative the fes

https://www.sciencedirect.com/science/article/abs/pii/S0167732220369336

With regard to observing the same numbers in different solvents, the only reason I can think at the moment is that the values are mostly dominated by the interaction of solutes.

I wonder if studying the structure of solvent after solvation using rdf or coordination numbers is helpful in your case, similar to what we did in the above-mentioned article.

Thank you all for your answers. I had an error in my calculation, which has been explained in gromacs forum:

https://gromacs.bioexcel.eu/t/what-the-vdw-and-coulombic-contributions-mean-in-a-solvation-free-energy-calculation/2690

the difference between energy of solution and solvent and solute

give the free energy of solvation

Hadi Jabbar Alagealy

Is the approach you suggest practically feasible?