[gmx-users] Free energy in octanol and water

[Gmx QA]

Hi gmx-users

I am trying to calculate the free energy of solvation for a drug-molecule
in octanol and water.

I am comparing two situations:

A: Two systems, one with the drug in water only, and one with the drug in
pure octanol.

B: drug in water only (same as in A), and then one box where I have added
20% water to my octanol system (since mixtures of octanol and water
typically contains some water in the octanol phase).

Then I run a series of free energy calculations per Justin's tutorial, 48
lambda points in total.
For system A I get a Delta-G for pure water of 39.07 kJ/mol, and 92.81
kJ/mol in pure octanol.

For system B, the Delta-G for pure water is the same, but for the
octanol-box with 20% water the Delta-G is 95.99 kJ/mol.

All of these results are obtained using gmx bar in gromacs 5.0.4.

My main concern is that the Delta-G is higher in the water/octanol mixture
than in pure octanol, but I would have expected the reverse to be the case?

Is there something wrong with my protocol? The forcefield is
GAFF/amber99sb,and all production runs are 10 ns in length.

Best
/PK

I have uploaded copies of all input-files here:

https://dl.dropboxusercontent.com/u/66785227/md.mdp
https://dl.dropboxusercontent.com/u/66785227/npt.gro
https://dl.dropboxusercontent.com/u/66785227/octanol_GMX.itp
https://dl.dropboxusercontent.com/u/66785227/API_gmx.itp
https://dl.dropboxusercontent.com/u/66785227/topol.top