Molecular docking with AutoDock Vina

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In this tutorial, we will show how to perform molecular docking thanks to the AutoDock Vina SAMSON Element that wraps the popular protein-ligand docking program AutoDock Vina (O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31 (2010) 455-461).

Requirements

Before starting the tutorial, please download the 2AZ8 file which contains protein-ligand complex used in this tutorial.

Tutorial

Launch SAMSON. Load the 2AZ8.sam file provided in the archive. It will open structural models of the HIV protease (2AZ8-A and 2AZ8-B) with a ligand (2AZ8-IA).

Let’s first add a secondary structure visual model for the protein. Select in the Document view 2AZ8-A and 2AZ8-B structural models, press Ctrl/Cmd⌘ + Shift + V (Visualization menu > Add visual model) and select the secondary structure visual model.

Note: if you cannot see the Document view, you can enable it in the Window menu, or by pressing Ctrl/Cmd⌘ + 1.

Now you can hide the 2AZ8-A and 2AZ8-B structural models by unchecking their boxes in the Document view.

Launching the AutoDock Vina app

Open the AutoDock Vina app by clicking on its icon . You can also find it in the App > Biology menu.

1. Setting up the system

Now we need to setup the receptor, the flexible side-chains, and the ligand.

Setup the receptor

Select the protein (2AZ8-A and 2AZ8-B) in the Document view and then press the Set receptor button.

Setup the flexible side-chains

If you want flexible side-chains, select them in the Document view or in the viewport, then press the Set flexible side-chains button. For simplicity, in this tutorial we will not be specifying the flexible side-chains.

Setup the ligand

Select the ligand (2AZ8-IA) in the Document view and then press the Set ligand button.

Setup rotatable bonds

If you have flexible side-chains, or a flexible ligand, you will see possible rotatable bonds in the viewport represented by green cylinders superimposed with bonds. Zoom in on the ligand (select the ligand in the Document view and then press Shift + Space).

Note: Having rotatable bonds makes the search slower but may result in more realistic docking.

You can activate or deactivate these rotatable bonds by clicking on the cylinders using the delegate editor . They will change colors when you switch their state. Green means the bond can rotate, and red means the bond cannot rotate.

For the sake of the tutorial, we will deactivate some rotatable bonds. Select the delegate editor then click on a rotatable bond

2. Setting up the search grid

The next step is to set the search grid. You can do it either by modifying the center of the grid and the size in the Element’s interface or using the delegate editor and dragging the yellow grid corners in the viewport.

3. Docking the ligand

Now we will set the exhaustiveness parameter and the maximum number of modes wanted:

  • Set the Exhaustiveness parameter (the higher the better, but the longer the search) to 100.
  • Set the Modes parameter (the maximum number of modes returned by the search algorithm) to 200.

Press the Dock button and wait for the results.

4. Visualizing results

As soon as the computations are done, the computed binding modes are generated both as structural models and conformations. You can hide all the generated structural models for the ligand by unchecking the box for newly created AutoDock Vina models layer.

To restore a conformation either double-click on the conformation in the Document view or right-click on the conformation node and in the context menu choose Restore conformation.

You can also select which mode to display by using the combo box in the Element’s interface.

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