[gmx-users] Ligand binding energy using LIE with PME

[David Mobley]

Diane,

> Also, some of my inhibitors and complexes are charged. In my simulation of the complex, I have added a counterion (Na). Does this complicate matters worse ? For the inhibitors in water, I protonated the ligand, according to a procedure I saw in a paper.

Ordinarily you want the system to be neutral, so the procedure is to
add counterions to make it neutral. It is a bad idea to protonate the
ligand, since the binding free energy is the free energy difference
between (P+L) and (PL), and, if one of those states has a protonated
ligand, it means you're actually computing the free energy between
(P+L') and (PL), where L' denotes the protonated ligand. This isn't
what one usually means by a binding free energy, and probably ends up
convoluting in the hydration free energy of your counterion.

It's far better just to make the system neutral in each state by
adding the same number of counterions, I think. Although I'm really
not a big fan of LIE and haven't used it much.

David