Calculation of Linear Interaction Energy (gmx lie)

GROMACS version: 2023.3
GROMACS modification: No

I am trying to calculate an estimate of the binding energy of a protein-ligand system through GROMACS by using gmx lie. I have two doubts:

a. My protein-ligand simulations were performed with a certain concentration of ions (K+, Na+, Cl- to balance electrostatic charges). Does the protein-only simulation require ions or can it be performed in water only? If no ions are to be used, how do I neutralize the system electrically?
b. Does the size of the periodic simulation box affect the calculation of LIE? Do the boxes have to be the same size?

Any feedback is greatly appreciated.