I'm Ben, I'm new here. I'm working on re-designing the binding pocket of an amino-acid binding protein for it to bind a new ligand. For this, I use enzdes. I want to compare the designs Rosetta makes with the wt protein in terms of binding energy (i.e. ligand-protein surface interaction energy) as a control. My question is: Is ligand docking the right application for this?
My plan in detail:
-Dock the wt ligand in the wt protein using water molecules as cofactors (trying to emulate the real binding mode, which includes water mediated contacts). I would use the ligand docking application with the relaxed (repacked) wt protein and no extra ligand rotamers (other than the crystallographic).
-Dock my new ligand in the wt protein using the water molecules that fit in there (not displaced by the new ligand) using the repacked wt protein and some ligand rotamers.
-Take my best design with the new ligand in it and check it's energy.
-Dock the wt ligand in the designed protein using some rotamers for the wt ligand.
Ideally, I will see that the new ligand in the designed protein has a similar energy to the wt ligand in the wt protein and the swapped structures are similarly disfavored.
Maybe there is a better way to do this that I'm not aware of, so I hear suggestions.