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
  • “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