# Solvation free energy calculation

**URL:** <https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation/9797>\
**Category:** User discussions\
**Tags:** free-energy\
**Created:** [August 1, 2024, 11:47pm UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation/9797 "2024-08-01T23:47:03Z")\
**Posts on this page:** 1\
**Showing post:** 2

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**Author:** ![MagnusL](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/magnusl/32/2380_2.png) [@MagnusL](https://gromacs.bioexcel.eu/u/MagnusL)\
**Post date:** [August 12, 2024, 8:39am UTC](https://gromacs.bioexcel.eu/t/solvation-free-energy-calculation/9797/2 "2024-08-12T08:39:41Z")

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With

```auto
couple_lambda0 = q
couple_lambda1 = none

```

you would definitely want to use soft-core for coulomb. But unless I’m completely mistaken `sc-coul` will not make any difference in this case. Just make sure that you have set the `sc-alpha` and the other soft-core parameters.

I might be wrong, but I think it’s only when using a setup like

```auto
couple_lambda0 = vdwq
couple_lambda1 = none

```

(or when using modifications in the topology) that `sc-alpha` makes a difference, i.e., if the soft-core parameters should be applied to both the vdw and q transformations.

I would recommend doing two sets of sequences of runs:

```auto
couple_lambda0 = vdwq
couple_lambda1 = vdw

```

and from the lambda 1 state output in that set of runs you run:

```auto
couple_lambda0 = vdw
couple_lambda1 = none

```

In theory, it is most efficient to run the respective lambda state simulations in each set in sequence, since you will then start each lambda state simulation from a state that is similar. But if you want to run very many simulations in parallel (better hardware utilisation) you will need to discard more time at the beginning of each simulation since it will take longer to reach equilibrium.

In the first of these sets you can set `sc-alpha = 0` since no soft-core modifications are needed when there are still vdw interactions. In the second you should set the proper sc parameters. `sc-coul` should not be necessary in either of these cases.

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