Hi,

I had a similar problem, with docking ligand to metalloprotein in AutoDock. You must change a metal chrge in the protein.pdbqt file. After create Your protein/receptor.pdbqt file You should edite this file in the text editor and change metal charge to the correct value and then save this change. For exemple Zn: from 0 to 2 or Mn 0 to 2. Next You should reload change file (if program ask about preserve charge You should press Yes button) and proceed with the docking procedure.

Hi,

Although the direct way would be open the pdbqt file and correct the charge from 0 to +n for a M(n+) ion, it won'b be realistic. If the ion is coordinated to different amino acids as ligands, the effective charge of the ion would be minor to the true value +n, due to charge transfer from the ligands. Trying to carry out docking calculations with fully charged metal ions will give you wrong poses or even increase the population of certain cluster a lot.

The best way to deal it is reparametrize the charges. You should perform a QM single point calculation of the coordination system, capping the amino acids adequetly. Then, perform a RESP fitting method to average the density charge over each atomic center. Now, you would obtain a more realistic charge over the metal center, which you should transfer to the pdbqt file. You should also transfer the charges of the amino acids implied in the coordination sphere as well, because it won't work if you also keep the original Kollman charges.

Follow this link to give you an initial idea: http://autodock.scripps.edu/news/successfully-docking-to-proteins-with-metal-ions/

Hope this help...

@Carlos Nieto

Sir, how to perform a QM single point calculation of the coordination system and capping the amino acids using a free software.

Dear Sindhuja,

Let's say you've got a L4Zn center, where L are amino acids coordinated tto the metal through lateral chain:

1) Cut the system from your protein (peptide bonds) and save as pdb.

2) Cap the amino acids. If you've got a N-terminal, put an acetyl group (-NH-COCH3).

Either your terminal is acid, put a methylamine (-CO-NHMe). With this, the calculation is performed over aminoacids where the amino and acid groups has peptide bonds, somewhat you are keeping the peptide nature of the amino groups, like the native protein.

3) Is your ligand docking at the metal? If yes, use QM to optimize the coordination phere with the amino acids and your ligand coordinated to the metal. Problably you've got a guess about how it binds to the metal. If the ligand is not binded to the metal, just perform a single point calculation. You should use a properly theory and basis set to cover metals (i.e PBE0/6-31G**). Use the below line at the input card to the gaussian .gjf file to calculate the electrostatic potential:

SCF=Tight Pop=MK IOp(6/33=2,6/41=10,6/42=17)

4) Use antechamber (AmberTools 14) to derive the resp fitted charges. You would obtain a mol2 file with the charges at the final column.

5) Try to repeat it in the abscence of ligand, and see how the charge changes with the ligand coordinated and not.

6) Translate the charges to your model. Some authors only translate metal charges and those of the atoms linked to the metal, instead of the overall residues. Check that the overall charge of the receptor in an integer. If not, redistribute the charge with autodocks option.

7) Other possibility is that the metal is out from the grid box. In that case, just skip all the above procedure and put the native charge of the anion (to save correctly the receptor pdbqt).

8) In theory, your docking results should be used to recalculate again the charges of the system, as you now would obtain a better docking pose (and if the results of coordination binding doesn´t match to the original idea when you had to perform the QM with your ligand).

Hope this helps...

thank you so much Sir.

Those related threads with answers by myself may help, too:

https://www.researchgate.net/post/How_can_we_change_the_partial_charge_of_a_pdbqt_file_in_autodock

https://www.researchgate.net/post/How_can_I_deal_with_metals_in_protein_using_autodock

How can I convert metal ion pdb/mol2 file to pdbqt using autodock?  

          When i convert its give following errors

Python 2.5.6 (r256:88840, Nov 6 2012, 15:29:26)

[GCC 4.1.2 20061115 (prerelease) (Debian 4.1.1-21)] on linux2

Type "copyright", "credits" or "license()" for more information.

****************************************************************

Personal firewall software may warn about the connection IDLE

makes to its subprocess using this computer's internal loopback

interface. This connection is not visible on any external

interface and no data is sent to or received from the Internet.

****************************************************************

IDLE 1.2.6 ==== No Subprocess ====

>>> cd+2:A:LIG:CD and cd+2:A:LIG:CD have the same coordinates

ERROR *********************************************

Traceback (most recent call last):

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/ViewerFramework/VF.py", line 898, in tryto

result = command( *args, **kw )

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/autotorsCommands.py", line 867, in doit

initLPO4(mol, cleanup=cleanup)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/autotorsCommands.py", line 292, in initLPO4

root=root, outputfilename=outputfilename, cleanup=cleanup)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/MoleculePreparation.py", line 1019, in __init__

detect_bonds_between_cycles=detect_bonds_between_cycles)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/MoleculePreparation.py", line 779, in __init__

detectAll=self.detect_bonds_between_cycles)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/MoleculePreparation.py", line 1798, in __init__

self.__classifyBonds(molecule.allAtoms, allow_guanidinium_torsions)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/MoleculePreparation.py", line 1836, in __classifyBonds

dict =self.dict = ADBC.classify(mol.allAtoms.bonds[0])

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/AutoDockBondClassifier.py", line 58, in classify

rotatables = self.d['rotatable'].select(bonds)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/MolKit/bondSelector.py", line 535, in select

rotatable = BondOrderBondSelector().select(bnds,1)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/MolKit/bondSelector.py", line 508, in select

atype.assignHybridization(allAts)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/PyBabel/atomTypes.py", line 137, in assignHybridization

self.valence_two()

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/PyBabel/atomTypes.py", line 266, in valence_two

angle1 = bond_angle(k.coords, a.coords, l.coords)

File "/home/garima/MGLTools-1.5.6/MGLToolsPckgs/PyBabel/util.py", line 47, in bond_angle

raise ZeroDivisionError("Input used:", a, b, c)

ZeroDivisionError: ('Input used:', [2.0, 0.0, 0.0], [2.0, 0.0, 0.0], [2.0, 0.0, 0.0])

Kindly provide me some ideas to overcome this problem.

Dear all,

I have a big metal sulphide cluster(nearly 2000 atoms with an average length of 5nm)and i want to dock a protein(whole protein pdb) as a ligand with the metal cluster.  I tried with autodock. But it took more time and display some error messages. Is there any way to do this? Kindly inform. Thanks in advance

Hi everybody,

Just wanted to point out that despite C. Nieto's proposed protocol is really nice and makes perfect sense as a general procedure for parametrizing structures before docking, I think it does not work when using Autodock Vina, since this program doesn't use charges.

Hope this helps

Few tricks be needed to carryout successfully completion.

1) Update the AD4_parameter.dat according to your necessary metal

2) Update the AD4.1_bound.dat also according to your necessary metal

3) then copy that two files into your installation folder

4) then during grid generation and docking dpf file generation steps, there at set map types option you should mention the required metal atom types and also there is a option named as other option; there u should mention the newly generated parameter file

5) finally the newly generated 2 files should be kept on your docking directory

Finally docking should successfully run.

Article AutoDock4(Zn): An Improved Auto Dock Force Field for Small-M...

http://autodock.scripps.edu/resources/autodockzn-forcefield

Hi

So we just need to treat metalloprotein with iron ion like other normal protein without metal ions since iron is already found in AD4_parameter.dat?