Protein-ligand docking


Continuing the discussion from Dealing with dimers:

For protein-ligand docking we do recommend modified settings for the docking, which do require guru access to the HADDOCK server. A tutorial describing protein-ligand docking can be download from the following link

Dealing with dimers
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unpinned #3


Dear all,

i would like to start a protein-ligand docking. Could I perform it through the haddock2.2 webserver?
My ligand is the oleic acid ? How can I upload the parameter to run the calculation?

Moreover I will not find anymore the tutorial for protein-ligand docking. Could someone send me the link
Thanks a lot
best regards
Francesca Cantini


Hi Francesca

Simply define the oleic acid as HETATM.

We have one protein-ligand tutorial online at:

Refer to the second part of the tutorial:


Thanks !!
Can I ask one thing about the file named clusters_haddock-sorted.stat_bestX ??

In this file the column named RMSD refers to the RMSD between the best X structures, while the column named RMSD-Emin is the RMSD from the lowest energy structure. It is ok ?



Yes it’s correct. With the lowest energy structure being the overall lowest (and not the lowest from that cluster)


Dear Alex
Just a question about protein-ligand interaction. I have following the tutorial and everything is ok but I have the following questions :
Do i need to scale down the intermolecular interactions for rigid body step ? from value 0.01 to 0? In order to ensure that the ligand would fit properly into the buried active site
If yes i do not remember which is the write parameter to change.
and I have to change something about The van der waals energy scoring for the rigid-body docking stage (w_vdw_0) ?
The ligand should be completely flexible ?

thanks a lot


If you have indeed a buried binding site you can run with scaling down interactions for rigid-body docking

Guru interface -> Energy and interaction parameters
(or for a local version, search for kinter in run.cns)

Scaling of intermolecular interactions for rigid body EM -> 0.01

And then change also the weight for the van der Waals it0 scoring (w_vdw_0) to 0.

I would also suggest to run with standard parameters (kinter=1.0), but upscale w_vdw_0 to 1.0
And take the best results of the two runs.

From our experience, it might be better to look at it1 models rather than water for small ligand (especially if hydrophobic and buried)
Also set the number of MD steps for the first two stage in it1 to 0.


OK thanks !


Dear Alex

Thanks for your suggestion, I have run the calculations as you told me and now I’m analyzing the results. I would like to ask you something, the reason why I obtain a value for restraints violation energy equal to 0.0 is due to the fact that I have used ambiguous restraints only in iteration 0 (rigid-body docking) ? as written in the protocol?



Hi Francesca

If you have only one restraint in the unambiguous caterogy (the ligand as active), any contact it makes in the binding site will result indeed in a 0 restraint energy.

Note that if you still have problems to reach the binding pocket you might even push kinter to 0.001


Dear all,

I’m running protein-oleic acid docking calculations, as the pKa of oleic acid is 4.99 and I’m working at pH 5, I would like to run two different calculations, one with oleic acid and one with oleate.

I started with two different PDB files of the ligand, one protonated and one deprotonated, but looking to the results and to the ligand,top file in the directory toppar I realized that in both calculations the ligand is deprotanated and have a charge equal to -1.

Could someone give me some suggestions?
thanks a lot


Hi Francesca

The server defines the parameters automatically using PRODRG (which ignores the hydrogens typically).
The only thing you could do is to take the results of the server, edit the ligand topology to change the charge state and run locally.

You might also try the new server from Jorgensen’s lab generating param/topo files for small ligand using the OPLS force field. The server now also support CNS-like output files.



Thanks I have tried the new server from Jorgensen’s lab and it generates several files , I have checked one of this file where the charges are reported and it is ok as my molecule now is neutral. Two questions: I presume that now I have to run the calculation locally?.
Which are the files that I have to used ? there are different format , but it seems to me that none are equal to , ligand.param
The server give me several files in these format CHARMM/NAMD; GROMACS ;PQR


Hi Francesca

I was too early in pointing to the new server - the version including the CNS parameters and topologies will go life in a few weeks.



OK I have tried to edit the ligand topology adding an hydrogen and changing the charge state. I’m trying to run the calculation locally. I have two questions : 1) in the PDB file of the oleic acid do I change “ATOM” with “HETATM” ?
2) in the run.cns I guess I have to change the topology and parameter files “” with those that I have generated for oleic acid “ and ligand.param”. I do not know what I have to introduce for " linkage file " .

thanks a lot


ATOM should work and indeed change the topo and param files for the ligand in run.cns

Note that the lig_par_gen server has been updated to output CNS parameters now.


OK thanks !!
Indeed I have a problem with the PDB ,

NBONDS: found 0 intra-atom interactions
%ATMCHK-ERR: unknown coordinates for atom " -202 -OLH -H54 "
%ATMCHK error encountered: Unknown coordinates
(CNS is in mode: SET ABORT=NORMal END)

ABORT mode will terminate program execution.

Program will stop immediately.

It seems that there is a problem with the PDB file or perhaps with my parameters.


Dear Alex
i was able to use the server that give the parameters file in CNS format. I run HADDOCK program but I encountered in this error:

PARRDR> if ( &BLANK%cofac_parameter_infile = false ) then
PARRDR> @@&cofac_parameter_infile
PARRDR>Remarks LigParGen generated XPLOR-TOP file for Bonvin group (by Leela Dodda)
PARRDR>set echo=false end
%PARRDR error encountered: exceeded MAXCP (PARAM) parameter --> recompile program
(CNS is in mode: SET ABORT=NORMal END)

ABORT mode will terminate program execution.

Program will stop immediately.

It seems that I have to recompile the program???

thanks for your help !