GROMACS version: All
GROMACS modification: No
Hi,
When one wants to compute the absolute binding free energy of a ligand to a protein, he/she needs to add restraints to keep the ligand in place when all interactions are set to zero. I want here to report something I was not expecting: it is currently not possible to only compute the free energy of adding these restraints with Gromacs, because in such a case couple-lambda0 and couple-lambda1 (in the mdp file) are both set to vdw-q and then Gromacs doesn’t want to go further.
Of course, we can circumvent this by using long vectors of lambda that take into account the addition of restraints and the removal of coulombic then vdw interactions. However, if for some reason we want to decompose the procedure it may be useful to be able to compute only the free energy of adding restraints. Perhaps there could be other options for couple-lambda0/couple-lambda1 ?
Nicolas