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PostPosted: Tue Jul 28, 2009 7:07 pm 
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Dear all,

I am a new user of AutoDock; I have a few questions, one about how partial charges are calculated, for ligand and macromolecule, during the preparation of the .pdbqt files., one regarding the issue of non integral charges on protein residues when partial charges are calculated and the last one regarding atoms in .pdbqt-protein files with 0.000 partial charge.

Question A)As I read in the tutorials the usual procedure to prepare .pdbqt files for macromolecule and ligand is to use AutoDockTools and do the following:


macromolecule:

1)Edit | Hydrogens | add all hydrogens

2)Grid | macromolecule | choose



...and AutoDockTools prepares the macromolecule automatically: partial charge calculation, merging of non-polar hydrogens, atom type definition...
During this automatic procedure are the partial charges calculated using gasteiger method or kollman? Isn't kollman the prefered method for proteins?

Ligands :

1)Add all hydrogens to the ligand.pdb file

2) Ligand |Input |open ligand.pdb


......and AutoDockTools prepares the ligand automatically: partial charge calculation, merging of non-polar hydrogens, atom type definition, torsion tree...During this automatic procedure are the partial charges calculated using gasteiger method or kollman? Isn't gasteiger the prefered method for ligands which are not peptides?

Question B) Recently I prepared the .pdbqt file for a protein doing the usual:

1)Edit | Hydrogens | add all hydrogens

2)Grid | macromolecule | choose


Unfortunately I received a Warning :


"Non integral charges on Protein"
"correct residues"

MET1
LYS327
SER340
and more...

"Charges should be corrected in written output file"

What can cause this kind of problem? Anyway to solve it I manually did:

1) Edit | Hydrogens | add all hydrogens
2) Edit | Charges | Add Kollman charges
3) Edit | Charges | Check totals on residues | spread Charge Deficit over all atoms in residue
4) Edit | merge non polar hydrogens
5) Atoms | assign AD4 type
6) File | save |write pdbqt


Do you think that this procedure is correct? should I add Gasteiger instead of Kollman partial charges? How important can these non integral charges be for the docking?

Question C)

I noticed that some atoms in the macromolecule pdbqt file have partial charge 0.000; I read in some tutorial that this can happen when AutoDock does not recognize the name of the atom/parent residue (and therefore can't retrieve the partial charge for that atom...); in my case this happens only for CB atom of GLU residues and CE2 atom of TRP residues...? Is there a way to find the partial charge normally given to these atoms?

Thank you very much for any help that you can give

kind regards

Frederick Daidone


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PostPosted: Wed Jul 29, 2009 1:10 am 
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For Vina, partial charges do not matter. For other purposes, the MGLTools forum may be more appropriate.

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If you don't get your question answered here, consider posting it on the AutoDock mailing list instead of this forum. Please do not email or PM me with requests for help.


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PostPosted: Sat Aug 08, 2009 11:05 am 
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Hi
Its an good approach which has been integrated in Vina. I was also not aware that for Vina Partial charges does not matter. so i have q queries in my mind could u answer hem for me.
1 - If it doest not require Partial Charges so It must be using there Inbuilt scripts for assigning charges. so which charges it use to calculate electristatic potential?
2- If Partial charges does not matter then why we use PDBQT as input file ?? It must be much more friendly if we have option to give PDB only.
Thanking You
Sushil


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PostPosted: Sun Aug 09, 2009 10:06 pm 
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Hi Sushil,

For 1): Vina neither uses nor calculates nor assigns partial charges at all, and however strange and unnatural this may appear, it still docks damn pretty good and fast. What matters is the quality of prediction, irrespective of how the prediction is made. Please re-check the Vina manuscript. Remember that AutoDock4 also docks very "unnatural": Nature certainly will not use a Lamarckian genetic algorithm to put a ligand into a receptor.

For 2): However, a regular pdb does not contain info about rotatable bonds. Plus pdbqt (with "t" of "atom type") is the same required input as in AutoDock4.

All the best,
WIM


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PostPosted: Tue Aug 11, 2009 4:28 pm 
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Hii
Thanks alot for your kind reply. I understand the things when i gone through your publication. I used this Vina last week, I feel that its comparatively fast and results were more better than my previous studies with autodock 3.0. I thank your group for this achievement. But now I have one question in mind which is related to Binding energy.
When i was using autodock3, I can compare binding energy obtained from autodock3.0 (about 9Kcal/mol) with the results from Isothermal Tritation Calorimetry and SPR experiments. Binding energy obtained in wet lab and by autodock was the same. But in Vina i am getting lower affinity values (6.1 Kcal/mol) for same set, perhaps ligand position is more accurate. Is there any way to get that values in way so that we can confirm the results from wet lab also.
Sincerely
Sushil


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