Difference between revisions of "AutoDock4/C2/Getting-Started-with-Docking/English"

Title Slide

Learning Objectives

• Download ligand and receptor files from the database
• Perform ligand refinement using AutoDockTools
• Prepare ligand for docking
• Save the refined ligand as a pdbqt file

System Requirement

Ubuntu Linux OS version 20.04

AutoDockTools version 1.5.7

Google Chrome browser version 96.0.4

And a working internet connection

Pre-requisites

basic computer operations, and

basic bioinformatics

Press Enter.

https://www.rcsb.org/

We will now download the ligand and receptor files from Protein Data Bank.

In the address bar type, rcsb.org

and Press Enter

Protein Data Bank website opens.

Type 2VTA in the search field.

Click on the search button.

Cursor on the page.

Click on the search button on the right.

The page refreshes with the 3D model and information about the protein.

2VTA codes for a Cyclin Dependent Kinase.

Click the Download Files button and select PDB format.

Click on the white triangle next to the button.

From the drop down options select PDB format.

Cursor on Small Molecules section.

Under Ligands ID, LZ1 click on Download Instance Coordinates, from the options in the drop down.

Choose MOL2 format, Chain D.

Click on the Download Instance Coordinates drop down.

From the options in the drop down, choose MOL2 format, Chain D.

Here is my Downloads directory.

Here are the two downloaded files from the PDB website, the mol file and the pdb file.

Use Ctrl + X key to cut and Ctrl + V' keys to paste the files.

I will select both the files and right-click.

From the options choose Move to option.

Select Move Destination window opens.

I will select my home folder and click on the Select button at the top-right corner.

We can alternatively use Ctrl and X keys to cut and Ctrl and V keys to paste the files.

Open AutoDockTools also called ADT .

I will open ADT using the terminal.

Type the system password.

Hence I will click on the Show Applications button at the bottom-left.

On the search bar that appears I will type Terminal.

Then click on the terminal option on the screen.

The terminal opens.

At the prompt I will type adt and press Enter.

Type the system password when prompted.

Click on File >> Preferences

>> Set.

In the Set User Preferences window, go to Startup Directory.

For me path is,

/home/snehalatha

ADT interface opens.

Set up your startup or working directory by going to File >> Preferences and then Set.

In the Set User Preferences window look for the Startup Directory field.

Here we need to set the path to the folder where we need to save the output files.

I am setting the path to my home directory.

Click on Make Default, and then click on Dismiss.

Choose Input and then click on the Open option.

Choose Input and then click on the Open option.

Click on the Open button at the bottom-right.

Since I have set the path for the home directory, the folder opens by default.

We need to open mol2 file.

So select Files of Type as Mol2 files from the drop-down.

Select the mol2 file of the ligand, 2vta_D_LZ1.mol2

Click the Open button at the bottom-right.

Cursor on the pop-up window.

Click on OK.

A popup window titled Summary for 2vta_D_LZ1 will appear.

The message with information about the structures will be displayed.

Read the message and note the information.

Click on OK button.

In the Add Hydrogens dialog box select radio button All Hydrogens.

Click on OK.

Cursor on the structure.

Click on the Edit menu, and select Hydrogens, then select Add option.

Add Hydrogens dialog box opens, select All Hydrogens radio button.

Leave all other settings as such and click on the OK.

You will now notice that hydrogens are added to the structure on the panel.

Adding Hydrogens

quantum mechanical optimization or

draw the 2D structure and convert to 3D in Open Babel.

In the above cases the hydrogens are automatically added.

Cursor on Write options dialog box.

Type the file name as Ligand.pdb

Cursor on Browse button.

Click OK to close the dialog box.

Go to File menu select Save option.

From the sub-menu select Write PDB.

Write options dialog box opens.

File name with .pdb extension and path to my working directory will be automatically populated.

Change the file name as Ligand.pdb

You can use the BROWSE button If you want to save in any other location.

Click OK to close the dialog box.

In the Quit dialog box, Do you wish to Quit?

click on OK.

Go to File menu and click on Exit option.

In the Quit dialog box, Do you wish to Quit?

click on OK button.

At the terminal prompt type adt and press Enter.

Click on “Remind me later” .

ADT window opens.

Click on Input then click on Open.

Since we have already saved the working directory, it is the default directory now.

Select Ligand.pdb, and click open.

Select Ligand.pdb, and click open button.

A pop-up window titled summary for Ligand will appear.

Read the message and click Ok to continue.

Cursor on the green sphere on nitrogen atom.

A green sphere will appear over the indazole Nitrogen atom.

This is the torsion root, or the center of rotation within the molecule.

This is a step to define the allowed torsions.

Cursor on Torsion Count dialog box.

All the bonds are red, cursor on bonds.

Click Done to close the window.

Click on Ligand, and select Torsion Tree then Choose Torsions.

Torsion Count dialog box opens.

This will change the color of all the bonds to demonstrate which are rotatable.

Here we see the number of rotatable bonds as Zero.

The parameters can be changed to fix the specific bonds.

Also allow additional degrees of freedom in ligand molecules.

Click Done to close the window.

A dialog box opens, file name is auto populated as ligand.pdbqt.

Click on Save button.

Click on Ligand, and select Output.

Then select Save as PDBQT.

A dialog box opens, file name is auto populated as ligand.pdbqt.

Click on Save button.

This completes the step of ligand refinement using AutoDock Tools.

Summary slide

In this tutorial we have,

Downloaded ligand and receptor files from the database.

Performed the ligand refinement using AutoDockTools.

Prepared the ligand for docking.

Saved the refined ligand structure as pdbqt file format using ADT.

Assignment

Read about the docking process.

Use the link given here for more information.

https://ccsb.scripps.edu/projects/docking/

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