AutoDock4/C2/Running-AutoGrid/English

Title of script: Running AutoGrid

Author: Dr.Snehalatha Kaliappan and Sruthi Sudhakar

Keywords: Autodock4, ADT, ligand, autogrid, macromolecule, pdbqt, video tutorial.

Visual Cue	Narration
Slide Number 1 Title Slide	Welcome to this spoken tutorial on Running AutoGrid.
Slide Number 2 Learning Objectives	In this tutorial, we will learn to, Set the grid box parameters Create a grid for the receptor molecule Save the grid box properties as .gpf file.
Slide Number 3 Learning Objectives	Run the AutoGrid program Check the output .glg file for the successful running of the AutoGrid program.
Slide Number 4 System Requirement	Here I am using, Ubuntu Linux OS version 20.04 AutoDockTools version 1.5.7 Gedit version 3.36.2 Windows users may use notepad or any other text editor.
Slide Number 5 Pre-requisites	To follow this tutorial learner should be familiar with, topics in basic bioinformatics basic operations on AutoDock Tools interface
Slide number 6 Code Files	The input files required for this tutorial are available in the Code files link. Please download and extract the files.
Slide number 7 Code Files	Save the input file in your home directory or working directory. Make a copy of all the files and then use them for practising
Open the terminal using “Show Applications” button. Type adt at the prompt. Cursor on ADT interface.	Here, I have opened the AutoDock Tools interface.
Cursor on the ADT interface.	I will open the session saved previously while preparing the receptor for docking. Please watch the pre-requisite tutorial on preparing the receptor for docking.
Click on File then Read Session, from the Read Pmv Session pop-up box, select, 2vta-receptor-prep.psf file. Click on Open button.	Click on File then choose Read Session. Read Pmv Session dialog-box opens. I will select the 2vta-receptor-prep.psf file which I had saved in my home directory. Click on the Open button.
Click on Grid tab on the menu bar. Click on Macromolecule and Choose option.	The model of the receptor molecule appears on the panel. To create the grid, click Grid tab on the menu bar. Select Macromolecule and click on Choose option.
In the Choose Macromolecule pop-up box, click on 2vta. Click on Select Molecule button at the bottom of the pop-up box.	In the Choose Macromolecule dialog-box click on 2vta. Click on the Select Molecule button at the bottom of the dialog-box.
Cursor on the pop-up window.	A WARNING pop-up window appears describing the following; * the number of non-bonded atoms, which ideally should be zero. * the number of non-polar hydrogen atoms found, and Note that the non-polar hydrogens, nphs have been merged.
Click OK Cursor on pop-up window Modified AutoDock4 Macromolecule File. Click on Save button.	Click OK to close the pop-up. Another pop-up window Modified AutoDock4 Macromolecule File opens. Save the receptor as a .pdbqt file. We need to use only the PDBQT file format for creating the grid. Click on Save button.
Cursor on the ADT panel.	Notice the change in the appearance of the receptor. The gasteiger charges are also calculated for each atom.
Click Grid then on Set Map Types, Open Ligand option. In the Ligand File window, select ligand.pdbqt file. Click on the Open button. https://docs.google.com/document/d/1zjUAaQkwaTQz1TYcASlQH7Pdw35u1jxvYJuJe5ZBKfQ/edit	Now let us add the ligand to the receptor. Next click Grid then on Set Map Types and Open Ligand option. A Ligand File window opens, select ligand.pdbqt file and click on Open button.
Cursor on the ADT panel.	You can now see that ligand added to the receptor. On the panel you can see receptor and ligand complex.
Cursor on the ADT interface.	Next we must prepare the grid box for this receptor-ligand complex. For this we must set the grid box parameters.
Slide Number 8 About Grid Box https://www.scripps.edu/sanner/software/adt/Tutorial/AutogpfTutorial.html The grid box set the boundary of the docking.	About the Grid Box. The grid box position defines the region of the receptor where the docking will be performed. Any region outside the box won't be explored during docking.
Slide Number 9 About Grid Box	However, we must first know the region of the receptor containing the ligand binding site. Learners must go through the literature for the information on the ligand binding site.
Slide Number 10 About Grid Box Learners please note: In case we do not know the exact coordinates for grid box, visualize the active site residues and set the grid boxes centering these residues. A blind docking covering the entire receptor can also be performed.	If the active site information is unknown, it is recommended to search all available surfaces. In such a case the grid box should cover the whole receptor-ligand complex.
Click Grid > Grid Box. Grid Options window opens.	Back to the ADT interface. To set the grid box, click on Grid then select Grid Box. Grid Options window opens. This will open up a menu-interface with some default options.
Cursor on the ADT interface.	On the panel you can now see the grid box covering a certain portion of the receptor. You will need to set the center of the grid as well as the x,y,z dimensions of the grid.
Cursor on the ADT interface.	Sometimes we may not know the active site information. In such a case a blind docking covering the entire receptor can also be performed.
Rotate the slider towards the right in x, y and z directions to reach 126 points. Cursor on the receptor-ligand complex.	In the Grid Options window, you can rotate the slider in x,y and z directions to cover the entire receptor-ligand complex. Click and drag the slider towards the right in x, y and z directions. Drag until you reach maximum capacity 126 points. As shown here we have the grid box covering the entire protein.
Cursor on the ADT interface.	In the present example, we already know the coordinates corresponding to the ligand binding site.
Rotate the slider towards the right on x, y and z direction to reach 50, (from 126 points to 50 points)	Rotate the slider to change the number of points on x, y and z directions to 50. Click the slider and drag the mouse from right to left to decrease the number.
Cursor on the ADT interface.	Observe the grid box, it is now smaller in size. Also observe that the grid box is not centered on the active site.
Change the numbers in the Center Grid Box. Change the Coordinates of the center of the binding site in the x, y and z direction to 27.86 , 0.69, 66.23. site-specific docking,	To center the grid box over the active site, change the numbers in the Center Gird Box. Change the coordinates of the center of the binding site in the x, y and z directions. I will type the numbers in the fields given. Type 27.86, 0.69, 66.23 in the x, y and z directions. Here too we can use the slider to change the numbers.
Cursor on the ADT interface.	Observe the panel, now the grid box is centered on the active site.
Click File in the top-left of the Grid Options window, choose Close saving current.	To save the grid box properties, click File in the top-left of the Grid Options window. From the options choose Close saving current. The Grid Options window closes.
Cursor on the ADT panel.	AutoGrid requires an input grid parameter file, which usually has the extension .gpf. The grid parameters you just set need to be saved as a .gpf file.
Click Grid on the main on the ADT interface, from the options choose Output. Select Save GPF. Grid Parameter Output File window opens.	Click Grid on the menu bar on the ADT interface., From the options choose Output. Select Save GPF. Grid Parameter Output File window opens.
Type the file name as 2vta.gpf. Click on Save button at the bottom-right in the Grid Parameter Output File window. Save the file as 2vta.gpf.	Type the file name as 2vta.gpf. Files of type field is already autofilled as gpf file. Click on Save button at the bottom-right in the Grid Parameter Output File window. The file will be saved in your home directory as 2vta.gpf.
click on Run on the toolbar. Choose Run AutoGrid from the drop down. Cursor on Run AutoGrid window.	To run AutoGrid, click on Run on the menu bar . Then choose Run AutoGrid from the drop down. Run AutoGrid window appears. Here you will notice that various fields are auto populated.
Cursor on Run AutoGrid window.	Windows users may click on the Browse button next to Program Pathname. They can then choose the location of autogrid4.exe.
Cursor on Run AutoGrid window.	Alternatively, you can copy and paste the autogrid4.exe file to your working directory. I am using Linux hence I will leave it as such as my Program Pathname is already auto-populated.
In the Run AutoGrid window, Click on the Browse button next to the Parameter Filename field. Select 2vta.gpf from the home folder. click on the Open button.	Next is Parameter Filename. I will click on the Browse button next to the Parameter Filename field. A autogrid4 Parameter File dialog box opens. I will select the 2vta.gpf from my home folder and click on the Open button.
Cursor on the Log Filename field.	Log Filename field will be automatically populated as 2vta.glg. Leave the rest of the parameters at the default setting.
Click on the Launch button. Cursor on the “Autodock Process Manager” window.	Click on the Launch button. A popup entitled “Autodock Process Manager” will appear. This popup will automatically close when the process ends.
Open home folder. Cursor on home folder. Cursor on .map files.	When the popup closes, AutoGrid has completed the generation of receptor maps. I will open my home folder and check for a number of files with the extension .map. Notice the number of files with .map extension. We also must locate the 2vta.glg file. Learners please note: Do not delete any of the output files generated during the running of the autogrid program. These files will be required for the next step, which is running of the autodock program.
Cursor on .map files. Right click on 2vta.glg file, choose, Open with Text Editor option. Scroll down the pages. Cursor on the line autogrid4: Successful Completion.	To make sure autogrid is successfully completed, open the .glg file with a text editor. Right click on the 2vta.glg file and choose, Open with Text Editor option. Scroll down the pages to the last line in the document. Here you can see the message, autogrid4: Successful Completion. Close the glg file.
Cursor on the .glg file.	This brings us to the end of this tutorial.
Slide Number 9 Summary Slide	Let's summarize, In this tutorial, we have, Set the grid box parameters Created the grid for the receptor molecule Saved the grid box properties as .gpf file
Slide Number 10 Summary Slide	Ran the AutoGrid program Checked the output .glg file for the successful running the AutoGrid program
Slide Number 10 Assignment	As an assignment Run the autogrid for the example, 1DWD given in the Examples folder in the Downloads page. https://autodock.scripps.edu/download-autodock4/
Slide Number 11 About Spoken Tutorial Project	The video at the following link summarizes the Spoken Tutorial project. Please download and watch it.
Slide Number 12 Spoken tutorial workshops	We conduct workshops using spoken tutorials and give certificates. For more details, please write to us.
Slide Number 13 Forum	Please post your timed queries in this forum.
Slide Number 14 Acknowledgement	Spoken Tutorial project was established by the Ministry of Education (MoE), Govt. of India
Slide Number 15 Acknowledgement	This tutorial is contributed by Snehalatha Kaliappan, Sruthi Sudhakar and Madhuri Ganapathi from IIT Bombay. Thank you for joining.

Contributors and Content Editors

Madhurig, Snehalathak