Tutorial - Docking a HIV Protease Inhibitor¶
Indinavir is a HIV Protease Inhibitor. Going to dock against...a HIV Protease (iPDB code of 1hsg).
Follow the PyRx tutorial to run a docking experiment, and carry out a virtual screen. The notes below give extra information (or corrections) on each step of the tutorial.
Note
Part 1 of the tutorial using AutoDock, but Part 2 uses Vina. Make sure you are using the correct wizard in each case.
Part 1 Exercise 1¶
- In the very first step, when you click Next, you need to wait about 2 minutes for the file to download
- Change address to http://pyrx.sf.net/sample.tar.gz
- (If that doesn’t work, choose local file and use sample.tar.gz)
- “Click on the arrow next to hsg1” should be...
- “Click on the plus sign next to hsg1”
- Note that using the Molecules tab you can...
- Display/hide a molecule
- Display/hide a particular chain
- Label a particular protein residue
- Can zoom with mouse wheel (after clicking on the 3D view)
- Full screen very useful (Esc to exit)
- Right click on a map (e.g. hsg1.A.map), and choose Display (MayaVi)
- In the MayaVi Panel, right click on Surface, and choose Hide/Show
- Right click on it again, and choose Add Module, Isosurface
- Once you are finishing, right click on IsoSurface, and choose Delete
Part 1 Exercise 2¶
- Choose “Local (requires local AutoDock binaries)” at the bottom of the screen
- (We have installed both Autodock and Vina locally)
Part 1 Exercise 3¶
- You will know when they are selected because it will list them at the bottom of the screen
- (as in the screenshot in the tutorial)
Part 1 Exercise 4¶
- Play around with the bounding box, then click Reset
- The Grids already exist, but let’s run AutoGrid anyway
- Instead of clicking Forward, click Run AutoGrid
- It takes around 30s
Part 1 Exercise 5¶
- Run AutoDock
- Takes about 5 minutes
- FYI:
- dlg = docking log file
- On Windows 7, all log files, etc. are placed in C:/Users/myname/.mgltools/PyRx
Part 1 Exercise 6¶
- Click on Binding Energy to sort the ligands
- The one with the most negative binding energy is the strongest binder
- You can right click on a row, and choose Creating Clustering Histogram
Part 2 Exercise 1¶
- Instead of opening “Desktop/PyRx2010/3D.sdf”
- Use 3D.sdf from here (download and save it on your Desktop).
- After you choose “Convert All to AutoDock Ligand”
- Right-click in the Ligands folder, and choose Refresh
- The list of ligands should appear
Part 2 Exercise 2¶
- When selecting the Molecules, instead of selecting them all, select only 5 or so.
- Each docking takes about a minute on these machines
- (You can ignore the text about computer clusters for this tutorial)
Part 2 Exercise 3¶
- ...we are not going to cover this now