Virtual High Throughput Screening (vHTS), also known as Virtual Screening (VS) is one of the essential steps involved in in-silico drug designing. There are several bioinformatics tools that facilitate the virtual screening of thousands of compounds such as GOLD, GLIDE, Autodock Vina, and so on.
Despite all the processing done by these tools, a basic methodology is required for vHTS of thousands of compounds present in a database. In this article, we are presenting a few basic steps required for performing structure-based VS using bioinformatics tools. The complete schema is presented in Figure 1.
Figure 1 Basic steps involved in virtual screening.
Step 1. Prepare receptor
Download the structure of receptor protein from PDB. In case, the structure is not available, predict the structure using homology modeling or ab-initio methods of structure prediction. Search the literature to gather information about the binding pocket or binding residues of the protein of interest. Select a chain (or two) consisting of the binding region. If the structural details are not available in the literature, then go for binding pocket prediction using webservers or tools.
Step 2. Download compound databases such as the ZINC database of small molecules.
Download the .sdf or .mol2 files of compounds. Some databases allow downloading only smiles of the compounds, then download the smiles and use a web server or software to convert these smiles into .sfd/.mol2 files.
Step 3. Prepare receptor and ligands for docking
Depending upon the software you are using for VS, prepare the files of the receptor protein and the ligands. for example, Autodock Vina requires receptor and ligand files in .pdbqt format.
Step 4. Run VS
Load all the files in the software and run VS. Wait for the results.
Step 5. Select drug-like compounds
Select the drug-like molecules based on the binding affinity and interaction with binding residues. You can also select some lead-like molecules showing less binding affinity.
Step 6. Filtering
You can further filter obtained drug-like molecules based on their toxicity, ADME properties, poses, and so on.
Step 7. Compound selection
Select potential drug candidates for further in vitro experiments.
These are the basic steps involved in VS for structure-based drug designing. There are several bioinformatics tools other than those mentioned above that are used in VS including Discovery Studio, LigandScout, and so on.
[Tutorial] Performing docking using DockingPie plugin in PyMOL.
How to install the DockingPie plugin on PyMOL?
DockingPie  is a plugin of PyMOL  made to fulfill the purpose of docking within the PyMOL interface. This plugin will allow you to dock using four different algorithms, namely, Vina, RxDock, SMINA, and ADFR. It will also allow you to perform flexible docking. Though the installation procedure is the same for all OSs, in this article, we are installing this plugin on Ubuntu (Linux).
[Tutorial] Installing Pyrx on Windows.
How to install Autodock4 on Ubuntu?
What values are considered as good or bad in computational docking?
How to sort binding affinities based on a cutoff using vs_analysis.py script?
Previously, we have provided a Python script (vs_analysis.py) to analyze the virtual screening (VS) results of Autodock Vina. Now, we have updated this script to sort binding affinities based on user inputted cutoff value. (more…)
Virtual Screening using Autodock Vina: Frequently Asked Questions & Answers for Starters
Virtual Screening (VS) is one of the important techniques in bioinformatics. It can be easily performed using Autodock Vina. We have provided detailed articles on this topic. In this article, we are trying to answer some FAQs for beginners. (more…)
[Tutorial] How to perform docking of zinc metalloproteins using Autodock Vina?
Proteins containing zinc atoms are docked in a different way than that of the normal simple proteins. Zinc atoms must be considered by a force field during the docking process. In this article, we are going to dock zinc metalloprotein with a ligand using Autodock Vina . (more…)
How to generate config file for docking using Autodock Tools?
How to install Autodock on Ubuntu (Linux) with CUDA GPU support?
Autodock  is most widely used for docking. To accelerate the docking process, especially, during virtual screening, Autodock-GPU  provides great help. In this article, we are going to install Autodock-GPU on Ubuntu. (more…)
Autodock Vina: Uses & Applications
Autodock Vina  is one of the most widely used bioinformatics software for computational docking. For beginners and those who are new to the field of bioinformatics, such software may appear confusing without having an initial idea of what this software actually used for. In this article, we have discussed some of the primary uses and applications of Autodock Vina software. (more…)
How to perform virtual screening using Pyrx?
How to perform metal ion-protein docking using idock?
How to install idock on Ubuntu?
idock  is a multithreaded software based on Autodock Vina. It is a virtual screening tool for flexible ligand docking. It also supports 27 different chemical elements including zinc, magnesium, iron, calcium, etc. In this article, we are going to install idock on Ubuntu. (more…)
How to analyze HADDOCK results using Pymol script generated from PRODIGY?
Installing PatchDock on Ubuntu (Linux)
PatchDock is a docking algorithm that is based on the shape complementarity principle [1,2]. It performs molecular docking of any two types of molecules including proteins, DNA, drugs, and peptides. In this article, we are going to install PatchDock on Ubuntu (Linux). (more…)
Protein-protein docking using HADDOCK2.4 web server
HADDOCK2.4 web server (https://bianca.science.uu.nl/haddock2.4/)  is used for protein-protein docking and their modeling. Not only proteins, but it can also process peptides, small molecules, and nucleic acids. In this article, we are going to perform protein-protein docking. (more…)
How to perform site-specific docking using Pyrx?
How to install sdsorter on Ubuntu (Linux)?
sdsorter is a tool that helps in the easy manipulation of SDF files. It takes a single file as input and also provides a single output file. In this article, we are going to install sdsorter on Ubuntu (Linux). (more…)