Closed AngelPineiro closed 1 year ago
Ritzhi-San
commented
1 year ago I believe from the error here, your flexible.pdbqt file was written incorrectly. There are specific tags the ligand.pdbqt and receptor.pdbqt must have to successfully start the docking prediction. If your source file is in the .pdb format, i highly suggest using autodock tools 1.5.7 (from the mgl tools suite here) to properly convert these files. Documentation on how to do this is also available online.
AngelPineiro
commented
1 year ago Before doing my own script for this I tried using MGLTools but then I have no control on which parts of my molecule are ridig and which are flexible. I followed the documentation of Vina to get my pdbqt and it seems correct to me. This cannot be so complex... I would really appreciate if someone could tell me which is the error in the lines I pasted in my original post.
El mar., 21 feb. 2023 1:29 a. m., Ritzhi-San @.***> escribió:
I believe from the error here, your flexible.pdbqt file was written incorrectly. There are specific tags the ligand.pdbqt and receptor.pdbqt must have to successfully start the docking prediction. If your source file is in the .pdb format, i highly suggest using autodock tools 1.5.7 (from the mgl tools suite here https://ccsb.scripps.edu/mgltools/downloads/) to properly convert these files. Documentation on how to do this is also available online.
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AngelPineiro
commented
1 year ago I found the error in the format: it seems that it cannot be 2 ROOT groups within the same residue. By grouping the atoms of the two ROOTs in the same ROOT I do not get the error. The correct format would be like this:
BEGIN_RES SBE3 1
ROOT
ATOM 6 C2 SBE3 1 44.590 47.130 29.260 1.00 0.00 0.232 C
ATOM 9 C3 SBE3 1 45.210 47.240 27.870 1.00 0.00 0.143 C
ATOM 12 C6 SBE3 1 41.770 48.010 26.090 1.00 0.00 0.232 C
ENDROOT
BRANCH 6 7
ATOM 7 O2 SBE3 1 45.450 47.350 30.390 1.00 0.00 -0.642 O
ATOM 8 H2 SBE3 1 45.190 46.740 31.150 1.00 0.00 0.410 H
ENDBRANCH 6 7
BRANCH 9 10
ATOM 10 O3 SBE3 1 46.210 46.210 27.830 1.00 0.00 -0.454 O
ATOM 11 C1X SBE3 1 47.490 46.740 27.450 1.00 0.00 0.311 C
ATOM 15 C2X SBE3 1 48.430 46.210 28.520 1.00 0.00 0.000 C
ATOM 16 C3X SBE3 1 49.880 46.660 28.300 1.00 0.00 0.000 C
ATOM 17 C4X SBE3 1 50.430 46.350 26.910 1.00 0.00 0.000 C
ATOM 18 SX SBE3 1 51.020 44.660 26.590 1.00 0.00 0.842 S
ATOM 19 O1X SBE3 1 51.010 44.520 25.100 1.00 0.00 -0.614 O
ATOM 20 O2X SBE3 1 52.380 44.490 27.200 1.00 0.00 -0.614 O
ATOM 21 O3X SBE3 1 49.990 43.750 27.190 1.00 0.00 -0.614 O
ENDBRANCH 9 10
BRANCH 12 13
ATOM 13 O6 SBE3 1 40.700 47.110 26.430 1.00 0.00 -0.642 O
ATOM 14 H6 SBE3 1 40.120 47.560 27.100 1.00 0.00 0.410 H
ENDBRANCH 12 13
END_RES SBE3 1 Now I have to see if the results are reasonable but at least I do not get the error in the format.
diogomart
commented
1 year ago Looks like the branch 9 10 block could use a few more rotatable bonds.
Not sure what your goal is, but you could take a look at meeko's docking covalent ligands as flexible sidechains, maybe it will be helpful.
AngelPineiro
commented
1 year ago Hi Diogo thank you very much for the suggestion. I took a look to the meeko package and it seems interesting but I think I cannot use it because my molecule is a bit large. What I have is a oligosaccharide that I build using my own code, typically it has between 300 and 600 atoms. I am trying to develop a code to have a reasonable docking approach for my specific molecules. Rigid docking provides reasonable affinity constants and structures, so I decided to include some level of flexibility. What I pasted in my previous posts is just one of the residues of my polymer, but I typically have 14-16. I guess Vina cannot manage all the torsions I would like to consider and this is why I decided to allow rotations just at the beginning of the relatively small chains representing mutations or sidechains in my molecule. The pdbqt arising from my code seems to work well (at least it does not provide errors and Vina is executed) but the resulting complexes and energies are quite unreasonable... worse than those obtaining from the rigid docking... I am working on this... so I would appreciate any advice.
On Tue, Feb 21, 2023 at 10:46 PM Diogo @.***> wrote:
Looks like the branch 9 10 block could use a few more rotatable bonds.
Not sure what your goal is, but you could take a look at meeko's docking covalent ligands as flexible sidechains https://github.com/forlilab/Meeko#docking-covalent-ligands-as-flexible-sidechains, maybe it will be helpful.
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diogomart
commented
1 year ago There are three categories of atoms in vina:
--receptor will not move at all--ligand will translate and rotate as a rigid body, plus rotation of rotatable bonds--flex rotation of rotational bonds, the atoms within the ROOT/ENDROOT block are fixed. This was designed for protein sidechains.There may be multiple ligands (in separate files), multiple flexible residues (in a single file), and one receptor.
Rotatable bonds rotate all atoms downstream of the ROOT atoms. Each rotatable bond is associated with a BRANCH/ENDBRANCH block. See the example here on page 29 of the AD4.2 manual. Note how BRANCH 6 7 is nested inside the BRANCH 1 6 block.
Hope this helps.
AngelPineiro
commented
1 year ago Yes, thank you for the help. Everything is working fine now with my code. I will explore now how to optimize the calculations but the results are reasonable now.
On Thu, Feb 23, 2023 at 6:03 PM Diogo @.***> wrote:
There are three categories of atoms in vina:
- --receptor will not move at all
- --ligand will translate and rotate as a rigid body, plus rotation of rotatable bonds
- --flex rotation of rotational bonds, the atoms within the ROOT/ENDROOT block are fixed. This was designed for protein sidechains. There may be multiple ligands (in separate files), multiple flexible residues (in a single file), and one receptor.
Rotatable bonds rotate all atoms downstream of the ROOT atoms. Each rotatable bond is associated with a BRANCH/ENDBRANCH block. See the example here on page 29 of the AD4.2 manual https://autodock.scripps.edu/wp-content/uploads/sites/56/2022/04/AutoDock4.2.6_UserGuide.pdf. Note how BRANCH 6 7 is nested inside the BRANCH 1 2 block.
Hope this helps.
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diogomart
commented
1 year ago Good to hear! I'll close, feel free to re-open if needed.
darekb94
commented
1 year ago @AngelPineiro > Yes, thank you for the help. Everything is working fine now with my code. I will explore now how to optimize the calculations but the results are reasonable now.
Dear Prof. Ángel Piñeiro, did I guess properly that the molecule you are dealing with is sulfobutyl ether beta cyclodextrin? If so, I would be very helpful for your advice. My goal is to dock small drug molecules into the cavity of this cyclodextrin. SBE side chains are very flexible so I am convinced that they should be treated as flexible parts of the receptor. I build the structure of SBE-b-CD manually in graphical moleular editor and thus obtained the pdb file without any headings such as ROOT or BRANCH. However, I cannot manage any flexible docking with this file, since I get the error: "IndexError: list index out of range". I cannot find the reason for this error and the issue I opened with a similar question ( #183) still remains unanswered. I wondered if it is only possible for macromolecules to ensure the flexibility of sidechains. However, your description shows that this is not the case. I would be very grateful if you could give me an advice how too deal with the flexibility of sulfobutyl ether sidechains. I would also ask if the results you obtained seem to be reasonable and the method of flexible docking can be succesful for the prediction of the affinities of a drug molecule to a cyclodextrin?
I want to do make a docking calculation with a non-standard molecule for which I am generating the flexible and ridid pdbqt files using my own scripts. After taking a look to the documentation I am testing Vina using the following flexible.pdbqt file:
but when I try to execute the docking calculation I get the following error:
I have no experience on docking, so I guess there is some obvious error but I cannot find it. I would appreciate any help.