I'm using the enzyme_design program to redesign an enzyme binding a ligand and have made an initial attempt to replicate the native structure. I've created parameter files for the two ligands (using the molfile_to_params.py script and setting --recharge=0 for each) and am using a resfile to indicate the atoms binding the ligand.
When I run the enzyme_design program, it generates results where large residues have been replaced with smaller ones (e.g. TRP -> GLY and PHE -> THR) and the ligand is not as tightly packed as in the native.
I've tried adding the ligpackerweight flag using values as high as 10, but this doesn't seem to have any effect.
I've also tried using the enzdes.wts file by using the flag:
but that also hasn't made any difference.
Are there any changes I can make that would encourage better packing of the ligand?