Virtual screening is used to identify small molecules that are most likely to bind to a target protein. There is various software available for virtual screening including GOLD [1] and GLIDE [2]. Autodock Vina [3] is a freely accessible software and provides good results can also be used for screening various ligands. Recently, Autodock Vina has provided plugins [4] to facilitate virtual screening. In previous articles, we have provided tutorials for the installation of Raccoon and Raccoon2 plugins on Ubuntu.

These plugins provide a graphical user interface and there is no need to prepare pdbqt files of protein and ligands. You can simply load your target protein and ligand pdb files. In this article, we will use a Perl script or a bash script to screen several ligands for a target protein.

Preparing input files

The docking procedure will be the same as mentioned in previous articles on site-specific docking and blind docking. (Video tutorials: site-specific docking and blind docking).

Prepare pdbqt files of the target protein and all ligands. You can also use OpenBabel software to convert them from sdf into pdbqt format. If you have downloaded smiles and want to convert them into 3D conformers then again use OpenBabel for that. For more details, read this article. Save them into the same directory.

Downloading scripts

For Ubuntu/Linux, download the following files from our Bitbucket account of Bioinformatics-Review or my personal account MunibaFaiza:

Perl script (vina_vs_linux.pl) and bash script (vina_vs.sh).

If you are using Perl script, then list the names of prepared pdbqt files of ligands in a text file.

If you are using the bash script, save the ligands pdbqt files as “ligand_name.pdbqt”, where the name could be any letter. For example, “ligand_3.pdbqt” or “ligand_hydrocl.pdbqt”, and so on.

Further, the configuration file will remain the same as mentioned in previous articles except for the second line, i.e., “Ligand = ligand.pdbqt”.  You can download the configuration file from here (change the coordinates as per your grid dimensions).

For Windows, download the following file from here or here:

Perl script (vina_vs_win.pl).

Running Vina for virtual screening

On Ubuntu:

Open the terminal (Ctrl+Alt+T) and type the following command:

$ perl vina_vs_linux.pl

It will prompt for the name of a file containing all the names of ligands. Enter the name of the file and continue.

or

$ ./vina_vs.sh

On Windows:

Open command prompt (type cmd in the search tab) and navigate to the folder where you have kept all files including vina.exe. Type the following command:

>perl vina_vs_win.pl

It will also prompt for the name of the file containing all the names of ligands. Enter the name of the file and continue.

or

> bash vina_vs.sh

Make sure you have already installed and added Vina in your path on Ubuntu. If not, then follow this tutorial.

References

1. Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997). Development and validation of a genetic algorithm for flexible docking. Journal of molecular biology, 267(3), 727-748.
2. Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., … & Shaw, D. E. (2004). Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of medicinal chemistry, 47(7), 1739-1749.
3. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455-461.
4. Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D. S., & Olson, A. J. (2016). Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nature Protocols, 11(5), 905-919.