Problem in screening compounds containing sulfate

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Problem in screening compounds containing sulfate

Postby zeta.tamimi » Mon Apr 28, 2014 2:41 am

Hello, My name is Zeta Tamimi from Faculty of Pharmacy University of Indonesia. I am in my 8th semester doing a research about In silico mechanism of some sea cucumber bio active compounds as anti-breast cancer using AutoDock and Vina.

I am having trouble during screening several bioactive compounds that I tested towards 5 target receptors (ER-alpha, FGFR1, IGFR1, PR, VEGFR2) in breast cancer using AutoDock, such as frondoside A, Holothurin A, Intercendensides A-C, okhotoside B1-B3, and 24-dehydroechinoside. All of them contains sulfate group.

There are two problems that are found during screening in AutoDock. First, AutoDock cannot process the screening because the selection molecules page object has no attribute tree (Figure 1). Second of all, I attempt to neutralist the compounds by reducing the sulfate group. The results is the compound shows binding energy except for the okhotoside B2 (Figure 3) and Okhotoside B3 (Figure 4). The AutoDock cannot found any docked conformation in those compounds (Figure 2).
Thank you for your attention and I am looking forward for your respond regarding to this case

Sincerely,
Zeta Tamimi
Attachments
figure 3.jpg
okhotoside B2
figure 3.jpg (26.43 KiB) Viewed 5764 times
figure 2.jpg
AutoDock cannot found any docked conformation
figure 2.jpg (110.3 KiB) Viewed 5764 times
figure 1.jpg
the selection molecules page object has no attribute tree
figure 1.jpg (100.47 KiB) Viewed 5764 times
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Re: Problem in screening compounds containing sulfate

Postby sargis » Tue Apr 29, 2014 12:47 am

Hello and thank you the message and figures. Using sea cucumber bio active compounds as anti-breast cancer drugs sounds interesting.

The first problem (object has no attribute tree) seems to be caused by upper case letters in 2OJ9_min. Rename this molecule to 2oj9_min before loading it to PyRx to see if that fixes this. I've made changes for upcoming 0.9.2 release of PyRx so that it can handle this case - https://sourceforge.net/p/pyrx/wiki/Changelog/

Regarding the second problem (AutoDock cannot found any docked conformation), try doing Open Babel energy minimization before making AutoDock ligand (pdbqt). If this doesn't work, increase the grid box size to see if that works.

Hope this helps and thank you for using PyRx!
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Re: Problem in screening compounds containing sulfate

Postby zeta.tamimi » Wed Apr 30, 2014 4:53 am

Hello Sargis, thank you for your help. I've tried the solutions that you have gave me. I still have problem during screening Okhotoside compounds. After minimize the energy and increase the grid box the results still the same. The AutoDock cannot found any docked conformation.

I wonder if all of the structure that I drew with Marvin sketch (2D) then I convert it to 3D with Marvin will affect the process screening in AutoDock.

Thank you for your attention

Sincerely,
Zeta Tamimi
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Re: Problem in screening compounds containing sulfate

Postby sargis » Wed Apr 30, 2014 4:14 pm

Hello Zeta. You are welcome. It would be interesting to see what the docking log file (dlg) looks like. Also, is Vina able to find any docked conformation for these compounds?

Sincerely,
Sargis
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Re: Problem in screening compounds containing sulfate

Postby zeta.tamimi » Fri May 02, 2014 9:02 am

Hello Sargis, I've already attached the dlg file. There is no problem doing screening in Vina for all of the compounds.

Thank you very much

Sincerely,
Zeta Tamimi
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1sj0_9_okhotoside_b2_nonion_mmff94_E=247.50_mmff94_E=246.17.dlg
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Re: Problem in screening compounds containing sulfate

Postby sargis » Sat May 03, 2014 2:52 am

Hello Zeta,

Thank you for the dlg file. I see from this file that AutoDock was compiled with maximum number of torsions set to 32, while your molecule has 34 active torsions:
C:\Program Files\PyRx\0.9.1\autodock4.exe: FATAL ERROR: PDBQT ERROR: too many torsions, maximum number of torsions is 32
C:\Program Files\PyRx\0.9.1\autodock4.exe: Unsuccessful Completion.

I have recompiled autodock4.exe with 40 MAX_TORS to handle this. Please unzip attached autodock4.exe and replace C:\Program Files\PyRx\0.9.1\autodock4.exe with the attached autodock4.exe.

You can also limit the number of active torsions when making pdbqt files using Edit -> Preferences -> AutoDock -> Ligand Preparation -> Number of torsion: option.

Please let me know if the attached autodock4.exe works for you.

Sincerely,
Sargis

PS: I used the info from the following links to make this autodock4.exe:
http://mgldev.scripps.edu/pipermail/aut ... 04969.html
http://www.mingw.org/wiki/FAQ
http://stackoverflow.com/questions/4702 ... is-missing
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autodock4.zip
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Re: Problem in screening compounds containing sulfate

Postby zeta.tamimi » Mon May 05, 2014 9:36 am

Hello Sargis,
I have unzip the autodock4.exe and replace C:\Program Files\PyRx\0.9.1\autodock4.exe with the attached autodock4.exe and it works successfully!

Thank you so much for your help. I really do appreciate it.

Sincerely,
Zeta Tamimi
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