Comparing Virtual Screening with Bioassays Using PyRx

Website - http://pyrx.scripps.edu
by Sargis Dallakyan, Ph.D.

Cheat Sheet / List of commands by Alex Perryman, Ph.D.

Click on the PyRx icon on the dashboard =

1.1 Importing Data into PyRx

(at the top, next to Python), File -> Import, select Workspace Tarball Remote File, click Next,
then click Finish. Wait for the Import Completed Successfully dialog and press OK.

Click on the arrow next to hsg1 to expand or contract the folders.

Double-click on a pdbqt file to show the molecule in a 3D Scene.

Control+click on any of the files in the AutoDock tab to obtain a menu of options with: Edit,
Delete, Properties, and Refresh commands.

Mouse Commands for PyRx

holding the left mouse button down and dragging will rotate the camera/actor in the
direction moved.
Holding down SHIFT when doing this will translate/pan the
scene just like holding down the middle button while moving
the mouse.

Holding down SHIFT and CONTROL and dragging up will

zoom in, while dragging down will zoom out. This is similar to
scrolling with the middle mouse button.

holding the right mouse button down and dragging upwards will zoom in (or
increase the actor's scale), and dragging downwards will zoom out (or reduce scale).
holding the middle mouse button down and dragging will pan the scene (i.e.,
translate the object).
Rolling the middle button upwards will zoom in, while downwards will zoom out.
Press the 'r' key on the keyboard to reset the camera's focal point and position (but not orientation).

1.2 Using the AutoDock Wizard

Under the Controls panel (in the middle/bottom half), click on the AutoDock Wizard tab
1.3 Selecting Molecules
(Helpful instructions are on the screen)

Select ind.pdbqt from the Ligands folder.

Select the hsg1 folder or the hsg1.pdbqt file from the Macromolecules folder.

Click Forward to go to the next exercise.

1.4 Running AutoGrid

In the 3D Scene, you will see a cube with a spherical handle on each face and one handle in the center.

Move the spherical handles of this cube to change the dimensions or center of the grid box.

Click the Maximize button to make the grid box encompass the entire target protein.

Click the Reset button to restore the original dimensions of the grid box.

Click Forward to continue.

1.5 Running AutoDock

This section utilizes the Run AutoDock tab.

Click on Docking Parameters... to see the run parameters that can be changed.

Click OK to close this run parameter window, then click Forward.

Since we already have sample, precomputed docking results to examine,

Click Forward to Analyze Results.

(If we didn't have precomputed results, then we would

Click Forward to Run AutoDock, instead).

1.6 Analyzing Results

The Analyze Results page displays the results of the docking calculations.

Click on the label at the top of a column (such as Binding Energy) to sort the table according to the
numerical values of the entries in that column.

Uncheck the box next to ind to un-display/hide the original, un-docked ligand

Click on a row to see a docked pose for that ligand in the 3D Scene.
***********************************************************************
Cleaning up, before beginning the next section:
Remove all the Files from the workspace
Click on the AutoDock tab in the Navigator window, and use Shift + the mouse to select all the files
in the Ligands folder. Right-click, select Delete, and click Yes to confirm.
***********************************************************************

Part 2: Comparing a Virtual Screen to PubChem's BioAssay Data

2.1. Preparing the Input Structures
Click on File -> Import, then click Next (for Molecule From Web)

Enter 2gdz for the PDB ID, and click Finish.

Right-Click on 2gdz in the Molecules tab, and select

AutoDock -> Make Macromolecule. Click OK.

Under the Controls pane (in the middle), click on Open Babel.

Click on the first icon on the toolbar (on the right, in the middle), which looks like a spreadsheet =

Open Desktop/PyRx2010/3D.sdf
If you can't find this file, you can download it from from the PyRx blog:
http://pyrx.scripps.edu/blog/81-thermal-shift-assay-for-inhibitors-of-hpgd

Right-Click on any of the entries inside the Open Babel widget.

Select Convert All to AutoDock Ligand (pdbqt).

2.2 Using the Vina Wizard

Under the Controls pane (in the middle), click on the Vina Wizard tab

Click the Start button (in the bottom, right corner) to begin.

On the Select Molecules page, use Shift + the mouse to select all the ligands (in the Ligands folder,
under the Navigator's AutoDock tab).

Select 2gdz under the Macromolecules folder, and then click Forward.

On the Run Vina page, click the Maximize button.

Click Forward to start the virtual screen.

Click on Analyze Results to see the VINA results as soon as they are created

Click on a Ligand's ID number to display the binding mode calculated by VINA (press the 3D Scene
tab to view the binding mode).
(Pause and wait for the Vina calculations to finish. Watch the ppt slides &/or ask questions)

2.3 Comparing Docking Results with Data from PubChem's BioAssay

Under the View pane (top-right corner), click on the Tables tab.

Click on the floppy disk icon on the toolbar =

to see how to save these tables as Comma-Separated Values files (CSV files). Press Cancel.

Click on the bar graph icon on the toolbar =

Under the Select Table heading, click the pull-down menu, and select Ligands.

Select Torsional DOF for the Y Column and Size for the X Column.

Click OK to store this figure under the 2D Plots tab.

On the Tables tab, click the folder icon =

Open Desktop/PyRx2010/BioAssay.csv
(which can also be obtained from the PyRx blog at
http://pyrx.scripps.edu/blog/81-thermal-shift-assay-for-inhibitors-of-hpgd

Click the bar graph icon again =

Under Select Table, choose Docking Results
Useful Resources
The Curious Wavefunction Blog - http://wavefunction.fieldofscience.com
In the Pipeline Blog - http://pipeline.corante.com

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