[modeller_usage] flexible ligand parametrization using nonstd_restraints(aln)

[Andrew Voronkov <>]

I have a task to remodel the loop conformation which binds ligand in order to optimize the ligand-protein structure. Structure is X-ray, but ligand position is not known, so I take it from docking assuming that docking gives pose  close to correct. So the goal is to model flexibility. I have asked this question couple of days a ago, but now it is more specific.
I have used loop modeling with lgiand transfer and it works relatively well, but as I understand as far as  this is non conventional residue it is treated as rigid and its interactions with protein are also treated as rigid according to what is written in the manual (listed below).
So is it possible to define ligand as flexible using nonst restrains, I need to consult with someone who did.
Actually it s kind of usage of Modeller as docking software, I don t knwo whether it is possible to parametrize ligand and optimize its position using simulated annealing and loop rmodeling, so kind of imitating induced fit. Has anyone tried this and question to Modeller Caretaker - is it potentially possible?

Best regards,
Andrew

nonstd restraints(aln)
44 CHAPTER 4. COMPARATIVE MODELING CLASS REFERENCE
This routine adds restraints to keep non-standard residues (anything treated as a HETATM or BLK residue,
such as ligands or metal ions) in a reasonable conformation. You can override this method if you need to
change these restraints.
By default, four sets of restraints are built:
• For each residue that has no defined topology (generally BLK residues, used to transfer ligands directly
from templates, as described in Section 2.2.1), intra-residue distances are all constrained to their
template values. This causes each residue to behave as a rigid body.
• Inter-residue distances are constrained to template values if these are 7°A or less. This has the effect of
preserving multiple-HETATM structures such as DNA chains. If the distances are 2.3°A or less they are
assumed to be bonds and so are restrained more strongly and also excluded from the nonbonded list.
• Residue-protein atom distances are strongly constrained to template values (and excluded from the
nonbonded list) if these are 2.3°A or less. This preserves chemical bonds between ligands and the
protein.
• Residue-protein C distances are constrained to template values if these are 10°A or less and are not
already bonded by the previous restraints. This preserves the ligand position.

- so I get protein-ligand interactions very much restrained and all final models are quite close to the initial coordinates.