Protein-ligand docking

HADDOCK
41

Hello all,

I’m going through the second part of this tutorial to do protein-ligand docking where I’m trying to use the provided GenTBL tool. However, every time I press ‘Submit’ at the bottom of the page, I get an Internal Server Error message. Can anyone explain what the problem might be or if I’m using the tool incorrectly?

Here are my inputs:
Selection 1 Active Residues: 101,104,105,111,114,115,139,143,191,192,195,196,198,199,202,203,229,265,266,279,282,283,286,292
Segment 1 ID: A
Selection 2 Active Residues: 1
Segment 2 ID: B

Thanks

42

Can you try:

http://alcazar.science.uu.nl/services/GenTBL/

Alse we recommend Chrome of Firefox for this.

43

Hi Alexandre,

Thank you for responding. Yes, that is the link I used. I tried submitting with both Chrome and Firefox, but I encounter the same error. Here is a screenshot:

image
image1309×273 23.1 KB

44

It should be working again. Please test.

45

Thank you so much, Alexandre! It works!

46

I tried using the LigParGen server because the PRODRG server renumbers atoms to names with a colon in it which CNS cannot handle. However, when using the TOP and PAR files from LigParGen, HADDOCK gives an “Error in the topology generation: prot_psf_mol2 could not be created” error. From generate_2.out the error causing this appears to be

%CODIMP-ERR: missing improper parameters
  improper energy constant missing.
  target improper value missing.
  periodicity missing.

which is very strange, because the TOP file by LigParGen does contain

{ Improper Dihedrals: aName1 aName2 aName3 aName4 }
IMPRoper C00 O01 O02 C03 
IMPRoper C05 C04 N06 C07 
IMPRoper C07 N08 C09 C05 
IMPRoper C03 C00 C0A C04
.... etcetera (27 IMPR lines total)

and the PAR file by LigParGen does contain

{ Improper Dihedrals: aType1 aType2 aType3 aType4 kt period phase }
IMPRoper C803   C800   O801   O802 10.50000 2 180.00000 
IMPRoper C807   C805   C804   N806 0.00000 2 180.00000 
IMPRoper C809   C807   C805   N808 0.00000 2 180.00000 
IMPRoper C810   C803   C800   C804 2.50000 2 180.00000 
... etcetera (27 lines of IMPR parameters total)

Some obvious differences between the TOP and PAR files from PRODRG and those from LigParGen are:

  • PRODRG chooses autogenerate angles=false while LigParGen uses autogenerate angles=true dihedrals=true. Can CNS/HADDOCK cope with having to autogenerate these?
  • The ligand contains 14 carbon atoms and 2 nitrogen atoms. The files from PRODRG thus contain 16 IMPR lines. The files from LigParGen list two IMPR lines for some carbon and nitrogen atoms, resulting in 27 lines. I wonder if this is the problem/inconsistency in the file. Am I right that only one improper angle per chiral atom is needed?

The GitHub for LigParGen seems abandoned, so I don’t know if it’s useful to try to contact the maker of LigParGen. It’s disappointing that this doesn’t work though, because the server is really easy to use.

47

tried using the LigParGen server because the PRODRG server renumbers atoms to names with a colon in it which CNS cannot handle.

Simple to edit the PRODRG param/top files if needed (especially if LigParGen is not working).

As for the error, you should look a bit higher in the file to see what is missing, i.e. for which combination of atoms.

48

Around the error in the generate_2.out file it says:

 %CODIMP-ERR: missing improper parameters %%%%%%%%%%%%%%%%%%%%%
  improper energy constant missing.
  target improper value missing.
  periodicity missing.
  ATOM1: SEGId="    ",  RESId="500 ",  NAME="C00 ",  CHEMical="C800"
  ATOM2: SEGId="    ",  RESId="500 ",  NAME="O01 ",  CHEMical="O801"
  ATOM3: SEGId="    ",  RESId="500 ",  NAME="O02 ",  CHEMical="O802"
  ATOM4: SEGId="    ",  RESId="500 ",  NAME="C03 ",  CHEMical="C803"
 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
 %CODIMP-ERR: missing improper parameters %%%%%%%%%%%%%%%%%%%%%
  improper energy constant missing.
  target improper value missing.
  periodicity missing.
  ATOM1: SEGId="    ",  RESId="500 ",  NAME="C05 ",  CHEMical="C805"
  ATOM2: SEGId="    ",  RESId="500 ",  NAME="C04 ",  CHEMical="C804"
  ATOM3: SEGId="    ",  RESId="500 ",  NAME="N06 ",  CHEMical="N806"
  ATOM4: SEGId="    ",  RESId="500 ",  NAME="C07 ",  CHEMical="C807"

this block of an error and the 4 atoms repeats 27 times, so these parameters are missing for every improper angle that was defined in the TOP file.

I am going to edit the PRODRG files indeed.