Multiwfn forum / Questions on how to rigorously measure free energies in solution

Re: Questions on how to rigorously measure free energies in solution

dummy@example.com (sobereva) — Tue, 20 Jan 2026 06:00:54 +0000

If you include "dG_solv + 1.89" into "E=" in settings.ini, then you do not need to manually add it to G_gas, otherwise you need to manually add them up.

Re: Questions on how to rigorously measure free energies in solution

dummy@example.com (wham09) — Tue, 20 Jan 2026 05:49:12 +0000

I would be really grateful if you could explain the answer to Q1 a little more. The way I understand is that the G in solvent phase is as below:
G_sol = G_gas + dG_solv + 1.89
Because G_gas = E_gas + dG_corr_gas,
G_sol = (E_gas + dG_corr_gas) + dG_solv + 1.89
Here, dG_corr_gas should be the correction for gas-phase G. Then, shouldn’t I actually put E_gas into Shermo to obtain G_gas first, and then manually add dG_solv and 1.89kcal/mol?

Re: Questions on how to rigorously measure free energies in solution

dummy@example.com (sobereva) — Tue, 20 Jan 2026 05:32:41 +0000

1 If you want to obtain G in solvent phase, you should put E_gas + dG_solv into settings.ini of Shermo, otherwise solvent effect will be missing.

2 The default grid (int=ultrafine for G16) is completely adequate.

3 When two energetic results will be compared with each other, or taking their difference, integration grid setting must be exactly the same.

4 It is true (at least for present purpose).

5 calc5 is meaningless. opt and freq tasks must be conducted at the same computational level (including the use of solvation model, which affects potential energy surface).

Questions on how to rigorously measure free energies in solution

dummy@example.com (wham09) — Tue, 20 Jan 2026 03:23:59 +0000

Dear Prof. Lu,

I did the following calculations for a ground-state molecule:

calc1. Geometry optimization (PCM model) + frequency calculation (B3LYP-D3(BJ) / def2-SVP, PCM)
calc2. Single point calculation (gas-phase) using calc1 geometry (B3LYP-D3(BJ) / def2-TZVP)
calc3. Single point calculation (gas-phase) using calc1 geometry (M05-2X / 6-31G*)
calc4. Single point calculation (SMD model) using calc1 geometry (M05-2X / 6-31G*, SMD)

From calc2, I obtained E_gas.
From calc3 and calc4, I obtained dG_solv.

If I understood correctly, the free energy is calculated as:
G = G_gas + dG_solv + 1.89
= (E_gas + dG_corr_gas) + dG_solv + 1.89

So I utilized Shermo on calc1 output for ZPVE scaling and msRRHO treatment, and obtained dG_corr_gas.
But here are my questions:

1. Am I correct to put E_gas (from calc2) into the Shermo's E value in the setting.ini file, rather than E_gas + dG_solv?

2. For calc3 and calc4 (using M05-2X functional), should superfine grids be used, as they sometimes should be for M06-2X?

3. In line with Q3, if I choose to do calc3 and calc4 using M06-2X instead, should I use superfine grids consistently?

4. calc1 was done with PCM because the geometry was sensitive to solvation. But then, is the Shermo result using the calc1 output truly the dG_corr_gas?

5. As an alternative, I did another frequency calculation (calc5) in the gas-phase using the calc1 geometry, but when I did this, I observed imaginary frequencies (expectedly). Would using Shermo on the calc5 output be more appropriate than using the calc1 output anyways?

6. Is there a truly ideal solution to Q4 and Q5? I don't care if it is cumbersome, I just want to know.

Thank you very much again for your time.