The main disadvantage of LIE is that one has to calibrate the scaling factors against experimental data specifically for the compounds being studied, which may be a problem given that
I have very limited access to experimental data at this point.
MM-PBSA/GBSA seems the most viable option here.Edit:
or, of course, MM-GBMV or MM-GBSW.
Or you could try FEP anyway, using CHARMM-GUI's new Ligand Binder feature. That should take some of the complexity out of it (but I don't know how stable and well-validated it is, and it's most probably still computationally expensive).