View source for AutoDock4/C2/Getting-Started-with-Docking/English

'''Title of script''':  '''Getting Started with Docking'''

'''Author''': Dr.Snehalatha Kaliappan and Sruthi Sudhakar.

'''Keywords''': autodock4, adt, mgl tools, ligand, receptor, rcsb protein data bank, ligand refinement, add hydrogens, detect root, rotatable bonds, pdb file, pdbqt file,  video tutorial.


{| border =1 
|-
|| '''Visual Cue'''
|| '''Narration'''
|-
||'''Slide Number 1'''

'''Title Slide'''
||Welcome to this tutorial on '''Getting Started with Docking'''.
|-
||'''Slide Number 2'''

'''Learning Objectives'''
||In this tutorial, we will learn to

* 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 

|-
||'''Slide Number 3'''

'''System Requirement'''
||Here I am using,

'''Ubuntu Linux '''OS version 20.04

'''AutoDockTools''' version 1.5.7

'''Google Chrome browser''' version 96.0.4

And a working internet connection

|-
||'''Slide Number 4'''

'''Pre-requisites'''
||To follow this tutorial learner should be familiar with,

basic computer operations, and 

basic bioinformatics

|-
||Open web browser, in the address bar type, '''rcsb.org''


Press Enter.

[https://www.rcsb.org/ https://www.rcsb.org/]
||Open any web browser. 

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.

|-
||https://www.rcsb.org/structure/2VTA


Type '''2VTA''' in the search field.


Click on the search button.


Cursor on the page.
||In the search field at the top, type the 4 letter '''PDB code 2VTA'''.


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'''. 

|-
||Cursor on the blue Download Files button.

Click the Download Files button and select '''PDB format.'''


||On the right-side of the page, you will see a '''Download Files''' button.


Click on the white triangle next to the button. 

From the drop down options select '''PDB format'''.

|-
||Show the pdb file, '''2vta.pdb''' in the '''Downloads''' folder.
||The PDB file '''2vta.pdb ''' for the protein '''2VTA ''' downloads to your '''Downloads''' folder.

|-
||Scroll down the page, 


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.'''

||Scroll down the page, in the '''Small Molecules ''' section under '''Ligands ID''' you will see '''LZ1'''.


Click on the '''Download Instance Coordinates ''' drop down. 

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

|-
||Show the mol file '''2vta_D_LZ1.mol2'''
||The mol file for the ligand downloads to the '''Downloads ''' directory in my system.


Here is my '''Downloads''' directory.


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

|-
||Click on the files '''2vta.pdb''' and '''2vta_D_LZ1.mol2'''.


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


||I will move both the downloaded files to my '''home directory'''.


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 the terminal using the show applications icon.
||The next step is ligand refinement.

Open '''AutoDockTools''' also called '''ADT''' .


I will open '''ADT''' using the terminal.
|-
||At the terminal prompt type '''adt '''and press Enter.


Type the system password.
||I am using the Ubuntu 20.04 system.

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.

|-
||Cursor on ADT interface.

Click on '''File''' >> '''Preferences''' 

>> '''Set'''.


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


For me path is, 


'''/home/snehalatha'''

|| Click on “'''Remind me later'''”.


'''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'''.

|-
||Click on the Ligand tab on the menu bar (last row in the menu bar)


Choose '''Input''' and then click on the Open option.

||To refine the '''ligand,''' click on '''Ligand ''' tab on the menu bar. 


Choose '''Input''' and then click on the '''Open''' option.
|-
|| In the '''Ligand file for AutoDock4''' , open '''2vta_D_LZ1.mol2 file'''.

Click on the Open button at the bottom-right. 

||The '''Ligand file for AutoDock4''' dialog box opens. 


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 display panel.

Cursor on the pop-up window.

Click on '''OK'''.
||The structure will appear in the display panel on the ADT interface.


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.
|-
|| Click on '''Edit''' menu, select '''Hydrogens''', then select '''Add''' option.


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


Click on '''OK'''.


Cursor on the structure.
||Since this structure was derived from the '''protein data bank''', it does not contain hydrogens.


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.

|-
||'''Slide Number 5 '''


'''Adding Hydrogens''' 
||This step can be ignored in cases where the ligand structure is generated by other means such as:

'''quantum mechanical optimization''' or 

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


In the above cases the hydrogens are automatically added. 

|-
||Go to '''File''' menu, >> '''Save''' >> '''Write PDB'''.


Cursor on''' Write options''' dialog box.

Type the file name as '''Ligand.pdb'''

Cursor on '''Browse''' button.

Click '''OK''' to close the dialog box.
||Now we have to save this structure in pdb format.


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.
|-
||Cursor on''' ADT''' interface.
|| Now we need to prepare the ligand for docking.

|-
||Close the window by File >> Exit

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

click on '''OK'''.

||Let us close the existing ADT window.

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.
||To open a new ''' ADT''' interface use the terminal as we did before.


At the terminal prompt type '''adt''' and press Enter.


Click on “'''Remind me later'''” . 

'''ADT''' window opens.

|-
||Go to '''Ligands''' menu >> '''Input''' >> '''Open'''.
||Go to '''Ligands''' menu.

Click on '''Input''' then click on '''Open'''.

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

|-
||Select '''Files of Type''' as '''PDB''' files from the drop-down.


Select '''Ligand.pdb''', and click '''open'''.
||Select '''Files of Type''' as '''PDB''' files from the drop-down.


Select '''Ligand.pdb,''' and click '''open ''' button.
|-
||Cursor on the adt display panel.
||The structure will appear in the display panel of '''ADT'''.


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

Read the message and click '''Ok''' to continue. 
|-
||Click '''Ligand''' >> '''Torsion Tree ''' >> '''Detect Root'''.

Cursor on the green sphere on nitrogen atom.

||Click '''Ligand and '''select '''Torsion Tree '''then choose '''Detect Root.'''

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'''. 

|-
||Click '''Ligand '''>> '''Torsion Tree''' >> '''Choose Torsions'''. 

Cursor on '''Torsion Count''' dialog box.


All the bonds are red, cursor on bonds.

Click '''Done '''to close the window. 
||To visualize which bonds are allowed to be rotatable, 


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. 
|-
||Click '''Ligand''' >>''' Output''' >> ''' Save as PDBQT'''.

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

Click on '''Save''' button.

||'''Save''' the file as a '''.pdbqt''' file. 


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'''.
|-
||'''Slide Number 6'''

'''Summary slide'''
||Let us summarize,


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'''.
|-
||'''Slide Number 7'''


'''Assignment'''
||As an assignment


Read about the docking process. 


Use the link given here for more information.


https://ccsb.scripps.edu/projects/docking/
|-
||'''Slide Number 8'''

'''About Spoken Tutorial Project '''
||
* The video at the following link summarizes the Spoken Tutorial project. 
* Please download and watch it. 

|-
||'''Slide Number 9'''

'''Spoken tutorial workshops '''
||
* We conduct workshops using spoken tutorials and give certificates. 
* For more details, please contact us. 

|-
||'''Slide Number 10'''

'''Answers for THIS Spoken Tutorial '''
||
* Do you have questions in THIS Spoken Tutorial? 
* Please visit this site 
* Choose the minute and second where you have the question. 
* Explain your question briefly 
* The spoken tutorial project will ensure an answer. 
* You will have to register on this website to ask questions. 


|-
||'''Slide 11''' 

'''Acknowledgement '''
||Spoken Tutorial project was established by Ministry of Education (MoE), Govt. of India 
|-
|| 
||This tutorial is contributed by Snehalatha Kaliappan, Sruthi Sudhakar and Madhuri Ganapathi from IIT Bombay.

Thank you for joining. 
|-
|}