Procedure

 

For more information about he software and other pre-requisites refer simulation tab.

Here one can perform rigid docking where the protein and the ligand molecule are non flexible. Here protein myoglobin (PDB ID - 1MBN)  is used as an example for receptor and its ligand HEM, which is renamed as "ligand" is used. 

 

1. Open the AutoDock software by clicking on AutoDock icon from your desktop. (Figure 1).

   

 

Figure 1: AutoDock GUI

 

2. Read the downloaded PDB molecule 3N7S in the work space panel by clicking on the tab “File“ and then select “Read molecules” as shown in Figure 2.

 

Figure 2: To read a molecule

 

Figure 3:  1MBN

 

3. PDB files can have errors such as missing atoms, chain breaks, water molecules etc. which is needed to be corrected. Select all water molecules which obstruct the accuracy of docking procedure.

 

4. Click on the “Edit” tab and select “Delete Water” to delete the water molecules from the receptor molecule as shown in Figure 4.

 

 

 

Figure 4: Deleting water molecule

 

5. For adding Hydrogens to satisfy valency, Click on the “Edit” tab and select “Hydrogen” and then select “Add” option as shown in Figure 5.

 

 

Figure 5 : Adding Hydrogen to the receptor

 

6. Now select “Polar Only” -> “noBondOrder”->”Yes” respectively and then click on the “Ok” option  as shown in Figure 6.

 

 

Figure 6: Adding Hydrogen

 

7. Click on the “Grid” option and select “Macromolecules” and select Choose option for selecting the molecule  as shown in Figure 7 and 8.

 

 

 

Figure 7 and 8: Selecting the receptor molecule for applying grid

 

8. By clicking on the respective molecule will display the details of non bonded atoms, non polar hydrogen atoms and non integral charge on the molecule. After that save the molecule in PDBQT format.(Figure 9)

 

 

Figure 9: Receptor molecule saved in PDBQT format 

 

9. To set grid parameters, go to “Grid” -> “Grid Box”  as shown in Figure 10. A “Grid Option” message appears which helps the user to change the grid point per map in all positions. It sets the 3D space for better binding conformation as shown in the figure. The maximum value that can be given by the Autogrid is 126.

 

 

Figure 10: Grid Option box

 

 

 Figure 11: Assigning 3D space for better binding conformation

 

10. Next step is to prepare the ligand molecule for docking. Open the ligand miolecule by clicking on the “Ligand” option and select “Input” and click on “Open”. Select the downloaded molecule and open it in the work space panel as shown in Figure 12.

 

 

Figure 12: Reading ligand molecule

 

 

 

Figure 13 : HEM opened in work space panel

 

11. The receptor molecule and ligand molecule can be viewed separately by clicking on dashboard which is displayed on the left side of the work space panel. By selecting the required molecule will display it in work space panel. The other options will enable us to view in other formats too  as shown in Figure 14. 

 

 

 

Figure 14: Dashboard with other options

 

12. To choose Torsions, click on the “ligand “ -> “Torsion Tree” ->”Choose Torsions” which will display the number of rotatable bonds. The rotatable bonds is displayed in green color, non-rotatable bonds in magenta color and unrotatable bonds in red color. To make a non - rotatable bond to rotatable, click on the bond itself  as shown in Figure 15.

 

 

Figure 15: Selecting torsions to view rotatable bonds

 

13. The output can be saved inPDBQT format. For that click on the “Ligand” -> “Output” ->”Save as PDBQT” , so that it can be saved along with the receptor molecule in the same folder itself  as shown in Figure

 

 

Figure 16: Output saved as PDBQT format

 

14.  For running the Vina program, command prompt is used, “vina help” prints the different options necessary for running the program. It includes commands for receptor, ligand and so on. The configuration file is wriiten in a text document with the following format as shown in Figure 17. 

 

 



Figure 17: Configuartion file saved as a text document

 

 

15. For running Autodock Vina, vina.exe --config conf.txt --log log.txt can be used as the script as shown in figure 14, which will create an outout file of the ligand and a log file along with other files. (Figure 18)

 

 

Figure 18: Output in Command prompt

 

16.

 

 

 

Figure 19 : Output opened in Pymol

 

This Experiment uses: Trott, O. and Olson, A. J. (2010), AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 31: 455–461. doi: 10.1002/jcc.21334,
onlinelibrary.wiley.com/doi/10.1002/jcc.21334/abstract