I’m using haddock3 to docking a ligand ensemble with 50 conformers into a very narrow pocket.The shape of the pocket looks like the letter " λ" and the reference ligand fills up the whole pocket.
Haddock refused to generate complex correctly because of the huge vdw repulsion in rigidbody step,even with a ±1 Å tolerence atom-level distance unambiguous restraint file.
I try to generate coords of the target ligands according to the same substructure atoms in reference ligand and fix it(mol_fix_origin_2=true) and the protein(mol_fix_origin_3=true,the first protein is free) in rigidbody step.But the ligand is not fixed.Most ligand conformers still tend to run away from the pocket.
Original coords(fig2) comparing with after rigidbody step(fig3).
I try to set inter_rigid = 0.001;w_vdw = 0.0 and a 0 Å tolerence atom-level distance unambiguous restraint file in rigidbody step and cancel them in flexref step, and it works for me(fig4).
So by setting mol_fix_origin_x=true, is it fixed at the very first time,but huge vdw repulsion dirves the ligand outside later in rigidbody step?Or something else happens?
I try to set inter_rigid = 0.001;w_vdw = 0.0 and a 0 Å tolerence atom-level distance unambiguous restraint file in rigidbody step and cancel them in flexref step, and it works for me(fig4).
That’s the recommended way to do it (described in some haddock2.4 tutorials)
So by setting mol_fix_origin_x=true, is it fixed at the very first time,but huge vdw repulsion dirves the ligand outside later in rigidbody step?Or something else happens?
You would have to fix both your receptor and ligand - but then effectively you are no longer doing the rigid body stage and can skip that module.
You might also try to follow our shape-docking protocol. There is an example provided.
It’s strange that I have fixed both receptor and ligand before,but the ligand still runs out of the receptor,unless I use strict tbl file and scale down inter-rigid vdw term.
I also learned shape docking before and success in some scenarios.But I mainly dock PRO-TAC system this week,where 2 separate protein carrying with 2 reference ligands,while my ligand is a linker connecting with 2 reference ligands.
Fixing 2 shapes and 2 proteins seems not suitable for PRO-TAC ligands,as the relative distance of the 2 proteins are unknown.
Since the terminal groups of PRO-TAC are exactly reference ligands from known PDB structure,defining corresponding distance restraints on PRO-TAC is easier for me.
