Losing Zinc metal in Macromolecule when converting to PDBQT

[GryderArt]

Faulty Macromolecule: when I open the PDB file, my enzyme macromolecule has a Zn in the active site. I can visualize Zn by right clicking ->Display ->Label ->Atom. However, once I create the PDBQT by right clicking -> Autodock ->Make Macromolecule, I lose the Zinc in the active site. The Zinc is obviously crucial to correct binding, since the ligand should chelate to it.

Anyone else have experience with this problem, or a solution?

Thanks!

[sargis]

Thanks for the message Berkley! I just tried this on 2XB3 and it kept Zn in PDBQT. In this case Zn atoms are in the main chain A. PyRx is using a script similar to prepare_receptor and it might be removing Zn atoms when there are part of a HETATM chain. Could you please attach your pdb or let me know where to get one to reproduce your case? Thanks!

[GryderArt]

Thanks for the message Berkley! I just tried this on 2XB3 and it kept Zn in PDBQT. In this case Zn atoms are in the main chain A. PyRx is using a script similar to prepare_receptor and it might be removing Zn atoms when there are part of a HETATM chain. Could you please attach your pdb or let me know where to get one to reproduce your case? Thanks!

It says the PDB file is too large to be attached. I will email it to you.

[GryderArt]

Turns out I can't find your email; please email me at berkley.gryder@gatech.edu and I will reply with 2 pdb files that are not available in the PDB (they have been determined/modified by groups in the field but not yet published)

[GryderArt]

I sent you an email using my @yahoo.com account; did you get it, or should I resend using my @gatech.edu account?

[sargis]

Thanks Berkley! I did get the email with the files attached. Thanks!

[M Indarte]

Hi there,

I was about to post a similar question. You can try these two ones in which my PyRx version (0.7) fails to generate the Mg++ or Ca++ atoms chelating the ligand:
3MMA
3EGZ

Any suggestions?

Thanks a million!

Martin Indarte

[sargis]

Turns out I can't find your email; please email me at berkley.gryder@gatech.edu and I will reply with 2 pdb files that are not available in the PDB (they have been determined/modified by groups in the field but not yet published)

Thanks Berkley! I checked the files and it removed Zn from pdb when Zn atom was not in the main chain A. As a quick fix, you can edit input pdb and replace chain ID from Z (last line) to A. When I read the modified pdb and created pdbqt for that, it worked fine (i.e. it kept Zn there).

I was about to post a similar question. You can try these two ones in which my PyRx version (0.7) fails to generate the Mg++ or Ca++ atoms chelating the ligand:
3MMA
3EGZ

Any suggestions?

Thanks Martin! In the case of 2EGZ, when I run Autodock ->Make Macromolecule it kept chain A only. What you can do to get pdbqt for both chains together is to run Autodock -> Make Macromolecule on each chain separately and then concatenate resulting pdbqt files.

Please let me know if you have questions or need more information.

Thank you gentlemen!!!

[GryderArt]

So even though I still dont know what caused the problem, I was able to get the PDB to not lose the metals by replacing HETATM with ATOM, and moving the TER line to the last row.

(This is for PDB named HDAC8_H_added)

From:

Code: Select all

ATOM   3390  CA  VAL A 377      66.006  75.107 -23.662  1.00 18.43           C 
ATOM   3391  C   VAL A 377      67.019  75.151 -24.794  1.00 18.49           C 
ATOM   3392  O   VAL A 377      66.659  74.991 -25.960  1.00 18.95           O 
TER    3393      VAL A 377
HETATM 3439 Zn    ZN A 388      59.980  70.647   4.956  1.00 26.10          Zn 
HETATM 3440 Ca    CA A 389      81.173  68.363 -19.143  1.00 25.54          Ca 
HETATM 3441 Ca    CA A 390      84.932  74.298  -2.867  1.00 60.05          Ca 
HETATM 3442 Na    NA A 391      69.041  75.550 -12.917  1.00 28.12          Na 
HETATM 3443 Na    NA A 392      59.007  71.319  -1.898  1.00 22.93          Na 


To:

Code: Select all

ATOM   3390  CA  VAL A 377      66.006  75.107 -23.662  1.00 18.43           C 
ATOM   3391  C   VAL A 377      67.019  75.151 -24.794  1.00 18.49           C 
ATOM   3392  O   VAL A 377      66.659  74.991 -25.960  1.00 18.95           O 
ATOM   3439 Zn    ZN A 388      59.980  70.647   4.956  1.00 26.10          Zn 
ATOM   3441 Ca    CA A 390      84.932  74.298  -2.867  1.00 60.05          Ca 
ATOM   3442 Na    NA A 391      69.041  75.550 -12.917  1.00 28.12          Na 
ATOM   3443 Na    NA A 392      59.007  71.319  -1.898  1.00 22.93          Na 
TER    3443 Na    NA A 392

Then when I created the PDBQT in PyRx, the Zn and other metals were not lost! Still doesn't make sense though because a similar file that had a zinc under "HETATM" wasn't lost...

Thanks so much Sargis and MI for your help!!

[M Indarte]

Cool, but I have not done more than bringing more headaches to this topic!

Anyways, I have noticed that when I convert a pdb (formal charges for Mg++ assigned MAESTRO) in PyRx I get the following message in the python shell:
Unable to assign MAP type to atom Mg
Sorry, there are no Gasteiger parameters available for atom 3egz_Mg++_nolig_model1: :MG 1:MG

Then, when I do docking of tetracyclynes (TCs) to the binding site seen in the X-ray (3egz) I do not see in many cases the classsical and strong TC-Me chelation, while I do see that TCs bind in a "crunched" position (box is roomy enough). This is a suggestion that the metal in the pdbqt file is seen more as a hindrance than as a blessing...

I am attaching the receptor pdb file which I am working with to see if there is a way to assign charges to the Me++ in PyRx or other ways to improve this.

Thanks for the input and suggestions!

M.