How to input 2 or more different small moleculers in haddock3 cfg file?

HADDOCK
1

Hi,I am using local haddock3 to do protein-ligand docking including 2 or more small moleculers.Here are 2 use cases I have met:

  1. some small moleculers are cofactors around the target,they need to be fixed in their original place.For example,in HADDOCK2.4 shape-restrained protein-small molecule tutorial contains ORO and FMN cofactors in protein.pdb and use tbl files to fix them.I try to reserve them in the protein structure pdb file in haddock3,but they are filtered after [topoaa] module.
  2. there are 2 ligands in different binding sites.I try to define them in [topoaa.2] and [topoaa.3] module but topoaa will failed to generate pdb files in [topoaa] directory.I don’t know how to define ligand_param_fname in rigidbody module either.

I try to convert one ligand into shape so that only one ligand needs to define top and param files in all modules.But I think this is not a good solution.Could haddock3 define multiple ligands in configure files?

2

Dear regen tsai,

To use ligands that are outside of the HADDOCK library, you need to provide both parameters and topology of those molecules to be able to use CNS related modules, such as [topoaa], [rigidbody], [flexref], etc…

For this, you need to use the ligand_param_fname and ligand_top_fname parameters in each module.

If you are dealing with multiple ligands, you can stack their parameters in the same file and topology in the same file.

Be aware that atom types definition and residue names MUST be different (and not overlap with already defined residues/atom types), otherwise it will create troubles.

I would suggest to generate those parameters either by downloading the haddock2.4 webserver run and use the generate parameters in haddock3, or to use CCP4-PRODRG to generate from PDB file. You can also try with the BioBB ligand parametrisation or ATB webserver.

For now, we do not have an easy/built-in way to create parameters/topology for ligands.

As an example of configuration file:

run_dir = "ligands_docking"
molecules = ["receptor", "ligand1.pdb", "ligand2.pdb"]
[topoaa]
ligand_param_fname = "combined_ligand1_ligand2.param"
ligand_top_fname = "combined_ligand1_ligand2.top"
[rigidbody]
ligand_param_fname = "combined_ligand1_ligand2.param"
ligand_top_fname = "combined_ligand1_ligand2.top"

You can also refer to examples we have on the github repository:

3

Thank you! I used to use acpype to generate CNS top and param files.Some of them can pass through topoaa modules,some can’t.I will try your suggestions and let you know whether this works.

4

It works to cat 2 top files and par files to do 4-body docking.Thank you!

test
test520×634 164 KB

1 Like