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e-LEA3D and ZODIAC PDF Print
Written by Sarkis Dallakian   

Thanks to Mark Fortner for sharing this article. It showed up today on my virtual screening feed from PubMed, but it's too good of an article to miss. Similar to AutoGrow, e-LEA3D is using fragments to built lead compounds. Building blocks are extracted from Comprehensive Medicinal Chemistry database by Symyx. It was interesting to find that besides DOCK Blaster there are also TarFisDock and SCFBIO servers that are using DOCK. Cloud Computing For Drug Discovery is an interesting subject and I knew that there are servers such as DockingServer, DrugFinder and GridSystems that are doing excellent job in this area. It's interesting also to mention that current version of e-LEA3D is using PLANTS for docking and Frog to generate 3D conformations. The most exciting part is that I rediscovered ZODIAC which is also a GUI for PLANTS. ZODIAC is very similar in spirit to PyRx in that it's an open source state-of-the-art tool for running molecular docking experiments. In summary, both e-LEA3D and ZODIAC are terrific tools for drug discovery.

 

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Last Updated on Thursday, 29 September 2011 09:30
 
ParaDockS PDF Print
Written by Sarkis Dallakian   

There is a new article in J. Chem. Inf. Model. that talks about ParaDockS. This is the only other docking program, besides AutoDock 4 and Vina, that is open source. Congradulations to ParaDockS team for making such a great product available! This means that PyRx can some day use ParaDockS and vise versa, so here I'll summirize main features of ParaDockS. First, it's using particle-swarm optimizer, similar to PSO@Autodock. Unlike, AutoDock 4, which uses force field-derived (AMBER) objective function, ParaDockS is using knowledge-based potentials. I look forward for the new develoments in this area.


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Last Updated on Thursday, 29 September 2011 09:30
 
List of Changes in PyRx Version 0.5 and Earlier PDF Print
Written by Sarkis Dallakian   

The following are list of changes in PyRx version 0.5 and earlier:

Version 0.5 - 25 March 2010

  • Added Save as Comma-Separated Values (CSV) tool for database tables.
  • Added plotting feature for database tables. This feature can be accessed through a toolbar button under Tables tab. By default, it opens up Table Plotting Dialog where a bar plot of Binding Energy versus Ligand (index) is shown. If you have PubChem BioAssay opened using open CVS button, this widget will also check to see if there is Outcome column in that table, and if so, it will color bars corresponding to "Active" compound red and bars corresponding to "Inactive" blue.
  • Changed default for maximum number of energy evaluations (generic algorithm parameter in AutoDock) from medium (ga_num_evals = 2500000) to short (ga_num_evals = 250000).
  • Added AutoDock PBS job submission progress dialog.
  • Fixed a bug that was causing problems when displaying molecular surfaces for docked conformations.
  • Added a dialog to select alternate conformation when making macromolecule file (pdbqt) for AutoDock.
  • Enabled Enthought's quality agent that can be used to get bug report and comments from a user.
  • Added Cancel option for AutoGrid Web Services.
  • Implemented flexible residues for AutoDock. This feature can be accesses by selecting residue(s) under Navigator -> Molecules and right-clicking on them. Select AutoDock -> Flexible Residues to create _flex folder under Navigator -> AutoDock -> Macromolecules with receptor pdbqt and flex.pdbqt. All docking to this receptor is then done with this flexible residue(s).
  • Updated Python to version 2.6 and ETS to 3.4.0.
  • The new installers delete previous installation folder, if any, before installing this new version.

Version 0.4 - 2 November 2009

  • Fixed TraitError: The 'cpu_num' (see Re: PyRx won't start).
  • Added AutoDockRemotePreferencesPage to allows users to change AutoDock and AutoDock service names. The defaults are set to Autodock_4.2.1 and Autodock_4.2.1.
  • Modified Remote Jobs Query in webSerives; it now updates the GUI after checking each job individually.
  • Made changes to AutoDockPage to make parsing and displaying docking results faster.
  • PyRx Table is populated when user clicks on that tab to speed up the startup time (see Re: How can I find the mistake).

Version 0.3 - 23 September 2009

  • When making AutoDock Ligands using Open Babel, it now logs problem causing cases.
  • Fixed Maximize action for Run AutoGrid page on AutoDock Wizard.
  • Local AutoDock executable paths can now have spaces in it.
  • Added splash screen.
  • Updated Enthought Tool Suite to version 3.3.0.

Version 0.2 - 20 June 2009

Version 0.1 - 23 April 2009

  • Fixed a couple of critical bugs including the one mentioned here.
  • Upgraded Enthought Tool Suite to version 3.0.2 and Open Babel to 2.2.1.
  • Added new AutoDock Execution Mode labeled Cluster (Portable Batch System) mode.

 

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Last Updated on Friday, 22 October 2010 13:26
 
Thermal Shift Assay for Inhibitors of 15-Hydroxyprostaglandin Dehydrogenase PDF Print
Written by Sarkis Dallakian   

Here are the results of a new PubChem BioAssay AID: 2427 with 42 compounds (22 active, 2 inactive and 18 inconclusive).

AutoDock did a perfect job here giving favourable binding energy for active compounds compared to inactives. As a result, we have a prefect ROC curve here. I made the makers bigger so you can see that all actives are on a vertical x=0 line and all inactives lay on a horizontal y=1 line.

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Last Updated on Thursday, 29 September 2011 09:32
 
qHTS Assay for Inhibitors of Dna Helicase PDF Print
Written by Sarkis Dallakian   

I've got another email from My NCBI (Subject: What's new for 'BioAssay - Limits: Protein 3D Structure). It was about AID: 2353 - qHTS Assay for Inhibitors of RecQ-Like Dna Helicase 1 with 23 active and 1272 tested compounds. There are 2 Links for Protein Structure corresponding to open and closed conformations. I run virtual screening for both of them, which produced similar results.

This looks more like an ROC curve you'll see in publications. In contrast to my previous results, this has fewer active compounds. One would think that AutoDock did a better job here since ROC curves are above the diagonal. However, as you can see from the plots on the left, lowest binding energies are coming from inactive compounds. The image below shows molecular surface for 2WWY (chain A) in green and lowest binding energy conformation for CID: 5328760 (-6.03 kcal/mol) and CID: 11957460 (-10.37 kcal/mol). The first one being the most active in the assay shows a weaker (virtual) binding compared to the second one, which although has the best computed binding energy is not active in the assay. The favourable binding energy is partally because of the size; CID: 11957460 is one of the largest in this assay. So the question is: what kind of changes needs to be done to virtual screening to make it agree more with experiment?

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Last Updated on Thursday, 29 September 2011 09:33
 
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