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How to perform blind docking using AutoDock Vina?

Dr. Muniba Faiza

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Blind docking is done when the catalytic/binding residues are unknown in a protein, hence, the binding pocket is unknown. In a previous article, we showed how to perform site-specific docking using Autodock Vina, where we bound a ligand in a catalytic pocket of a protein. Now, this article will cover the blind docking using Autodock Vina.

We are docking the same protein Human Serum Albumin (HSA) with a ligand Sodium Octanoate (SO) but since the HSA is already complexed with 3-carboxy-4-methyl-5-propyl-furanpropanoic acid (CMPF), therefore, it should be removed first leaving the only protein.

As mentioned previously, we need the following files prepared for docking with AutoDock Vina:

  1. Pdbqt files of protein and the ligand
  2. Configuration file
  3. Grid file

 

Preparation of PDB file before docking

  1. Download a protein crystal structure from PDB. We are using Human Serum Albumin complexed with 3-carboxy-4-methyl-5-propyl-furanpropanoic acid (CMPF) (PDB ID: 2BXA).
  1. Open the PDB file and remove HETATOMS.

The structure we are using is a crystal structure complexed with a ligand, therefore, in order to know the binding position of our ligand, we need to empty all the binding pockets by removing the bound ligand which can be done by deleting all hetatoms from the PDB file. If we will dock our ligand without removing the already complexed ligand, then we will not get the correct results. We can also easily remove ligand by visualizing the protein in PyMol.

  1. After removing hetatoms, we will keep only one of the four chains (here, Chain A was taken) and remove the rest of the three chains and save this file as “protein.pdb”

The chains are removed from the protein structure just to avoid complexity. But remember to read about the structure of your protein to know what chains are necessarily involved in the protein functioning.

  1. Now save the file as “protein.pdb”.

Now we have prepared our protein structure to proceed further for docking. Now we will prepare our ligand which we want to dock with the protein.

Preparation of ligand before docking

  1. Open PubChem (www.pubchem.ncbi.nlm.nih.gov) and search for the compound. We are using “sodium octanoate” as a ligand. We can download the structure from the ZINC database also.
  2. Click on Sodium octanoate and look under “3D Structure” section, click on “Download” and then you will see four different formats for downloading it. We will download the .SDF format.
  3. Since we need the protein and the ligand to be in a .pdb format, therefore, we have to convert .SDF to .pdb. We will use PyMol for this purpose and never use online converters because they may ruin your ligand file.
  4. Open PyMol, and open the downloaded ligand. Click on “File” –> “Save Molecule” –> select the molecule –> click “OK”. You can save it to your desired folder.

We will rename the ligand as “SO.pdb” just to avoid any kind of confusion. Now we have a PDB file of protein and that of the ligand. In order to perform docking, we need to prepare .pdbqt files from the .pdb files of the protein and the ligand, because docking through AutoDock Vina requires .pdbqt file format to dock.

Preparation of .pdbqt files

First, we will prepare a .pdbqt file of the ligand.

  1. Open AutoDock Vina –> click “Ligand” –> click “Input”–> click “Open”

It will ask to select your ligand, we will go to the folder where we have saved our ligand’s .pdb file and click “SO.pdb”.

  1. Click “Ligand” –> click “Torsion Tree” –> click “Detect Root”.

It will show the torsion angle on the ligand from where it can be rotated.

  1. Click “Ligand” –> click “Output” –> Click “Save as PDBQT”.

We can rename the ligand, but we will use the same name as before and will name it as “SO.pdbqt” and save it in the same folder.

We have prepared a .pdbqt file of the ligand and now we will prepare the protein file.

  1. Open AutoDock Vina, click “File” –> click “Read Molecule” –> select protein.pdb.
  2. We will delete water molecules from the protein as they can make unnecessary bonds with the ligand. Click “Edit” à click “Delete water”.
  3. We will add polar hydrogens in order to avoid any empty group/ atom left in the protein. Click “Edit” –> click “Add Hydrogens” –> click “Polar only”.
  4. We will save this file as .pdbqt, click “Grid” –> click “Macromolecule” –> click “Choose” –> select the “protein.pdb” –> click “OK”. It will ask for a folder to save, then save it as “protein.pdbqt”, in the same folder where the pdbqt file of the ligand was saved.

Again, since it is a tutorial for blind docking, there is no need to define binding residues.

Defining Grid Box for docking

In blind docking, we do not need to define a specific site in the protein for the ligand to bind, because we do not know the binding site, so we enclose the whole protein into the grid box. Make sure the whole protein fits inside the grid box.

  1. Click “Grid” –> click “Grid Box”.

You will see a small window in which you can see x, y, and z coordinates.

  1. Now try to adjust the grid box by scrolling the three coordinates, such that it covers all the selected residues.
  2. After adjusting the grid box, click “File” –> click “Output Grid Dimension File” –> save this file as grid.txt in the same folder.
  3. Click “File” –> Click “Close saving current”.
  4. Now close the Autodock Vina.

You will get the grid file as follows:

                  grid.txt

protein

spacing    0.375
npts       66 56 54
center     4.402 -8.060  8.874

Preparation of Configuration file

AutoDock Vina requires an input configuration file which contains all the information of the parameters used in configuring the docking including the name of the protein and the ligand. The configuration is as follows:

                                    conf.txt

receptor= protein.pdbqt

ligand= SO.pdbqt

 

center_x= 0.430

center_y= 6.575

center_z= -0.235

 

size_x= 72

size_y= 94

size_z= 72

 

out= vina_outSO.pdbqt

log= logSO.txt

 

exhaustiveness= 8

From “grid.txt” file, we have written the center_x, y, and z coordinates, and also the size_x, y, and z of the grid box. Save this file as “conf.txt”.

Perform Docking

Put all the following in the same folder (i.e., dock):

  1. protein.pdbqt
  2. SO.pdbqt
  3. conf.txt
  4. All the MGL_Tools, Autodock Tools, Python.exe (for Linux) and Autodock Vina setup files.

Please keep in mind that you have named the files properly and kept all the setup files in the same folder otherwise you may get errors while running the docking.

Linux

  1. Open the terminal and enter into the “dock” folder.
  2. Type the following command:
./vina -–config conf.txt -–log logSO.txt
  1. Press “enter”.

Windows

  1. Open the command prompt and enter the folder where all the docking files are placed.
  2. Type the following command:
 vina -–config conf.txt -–log logSO.txt

Vina Output

After the successful docking, you will get a log file, which in this case is named “logSO.txt”.

The log file will look like this:

 

This file consists of all the poses generated by the AutoDock Vina along with their binding affinities and RMSD scores. In the Vina output log file, the first pose is considered as the best because it has more binding affinity than the other poses and without any RMSD value, but you can choose the appropriate pose and visualize it in PyMol viewer.

Please share if you like this article!

If you have any query, then feel free to contact me at [email protected].

Reference

  1. 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 chemistry31(2), 455-461.

 

Dr. Muniba is a Bioinformatician based in New Delhi, India. She has completed her PhD in Bioinformatics from South China University of Technology, Guangzhou, China. She has cutting edge knowledge of bioinformatics tools, algorithms, and drug designing. When she is not reading she is found enjoying with the family. Know more about Muniba

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Bioinformatics Programming

DockingAnalyzer.py: A New Python script to Identify Ligand Binding in Protein Pockets.

Dr. Muniba Faiza

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DockingAnalyzer.py-A Python script to identify ligand binding in protein pockets.

High-throughput virtual screening (HTVS) is a pivotal technique in drug discovery that screens extensive libraries of compounds to find potential drug candidates. One of the essential tasks in HTVS is to ensure that ligands are binding within the protein’s binding pocket. This task can be particularly challenging when dealing with thousands of docking results. To address this challenge, we present a Python script that automates the analysis of molecular docking results generated by AutoDock Vina [1] using PyMOL [2]. This script calculates the center of mass (COM) for each docked pose, compares it with a reference ligand’s COM, and identifies poses that bind within a specified threshold distance. This process is crucial in mass docking scenarios where confirming ligand binding within the pocket is necessary. (more…)

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Bioinformatics News

VS_Analysis: A Python package to perform post-virtual screening analysis

Dr. Muniba Faiza

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VS_Analysis: A Python package to perform post-virtual screening analysis

Virtual screening (VS) is a crucial aspect of bioinformatics. As you may already know, there are various tools available for this purpose, including both paid and freely accessible options such as Autodock Vina. Conducting virtual screening with Autodock Vina requires less effort than analyzing its results. However, the analysis process can be challenging due to the large number of output files generated. To address this, we offer a comprehensive Python package designed to automate the analysis of virtual screening results.

(more…)

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Bioinformatics Programming

vs_interaction_analysis.py: Python script to perform post-virtual screening analysis

Dr. Muniba Faiza

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vs_interaction_analysis.py: Python script to perform post-virtual screening analysis

Analyzing the results of virtual screening (VS) performed with Autodock Vina [1] can be challenging when done manually. In earlier instances, we supplied two scripts, namely vs_analysis.py [2,3] and vs_analysis_compounds.py [4]. This time, we have developed a new Python script to simplify the analysis of VS results.

(more…)

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Docking

[Tutorial] Performing docking using DockingPie plugin in PyMOL.

Dr. Muniba Faiza

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[Tutorial] Performing docking using DockingPie plugin in PyMOL.

DockingPie [1] is a PyMOL plugin to perform computational docking within PyMOL [2]. In this article, we will perform simple docking using DockingPie1.2.

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Docking

How to install the DockingPie plugin on PyMOL?

Dr. Muniba Faiza

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How to install DockingPie plugin on PyMOL?

DockingPie [1] is a plugin of PyMOL [2] 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).

(more…)

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Docking

[Tutorial] Installing Pyrx on Windows.

Dr. Muniba Faiza

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[Tutorial] Installing Pyrx on Windows.

Pyrx [1] is another virtual screening software that also offers to perform docking using Autodock Vina. In this article, we will install Pyrx on Windows. (more…)

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Docking

How to install Autodock4 on Ubuntu?

Dr. Muniba Faiza

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How to install Autodock4 on Ubuntu?

Autodock suite is used for docking small molecules [1]. Recently, Autodock-GPU [2] is developed to accelerate the docking process. Its installation is described in this article. In this tutorial, we will install Autodock 4.2.6 on Ubuntu.

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Docking

What values are considered as good or bad in computational docking?

Dr. Muniba Faiza

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After performing computational docking, a question that comes to mind most is “what docking score is considered good or bad”. In this article, we will discuss this in detail. (more…)

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Bioinformatics Programming

How to sort binding affinities based on a cutoff using vs_analysis.py script?

Dr. Muniba Faiza

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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…)

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Docking

Virtual Screening using Autodock Vina: Frequently Asked Questions & Answers for Starters

Dr. Muniba Faiza

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Virtual Screening using Autodock Vina: Virtual Screening: 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…)

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Docking

[Tutorial] How to perform docking of zinc metalloproteins using Autodock Vina?

Dr. Muniba Faiza

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[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 [1]. (more…)

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Docking

How to generate config file for docking using Autodock Tools?

Dr. Muniba Faiza

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How to generate config file for docking using Autodock Tools?

A configuration file is one of the required files for docking using Autodock Vina. In this article, we are going to generate a config file using Autodock Tools GUI [1]. (more…)

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Docking

How to install Autodock on Ubuntu (Linux) with CUDA GPU support?

Dr. Muniba Faiza

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How to install Autodock on Ubuntu (Linux) with CUDA GPU support?

Autodock [1] is most widely used for docking. To accelerate the docking process, especially, during virtual screening, Autodock-GPU [2] provides great help. In this article, we are going to install Autodock-GPU on Ubuntu. (more…)

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Docking

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Autodock Vina: Uses & Applications

Autodock Vina [1] 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…)

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Docking

How to perform virtual screening using Pyrx?

Dr. Muniba Faiza

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How to perform virtual screening using Pyrx?

Pyrx is a bioinformatics tool to perform virtual screening [1]. We previously provided an article on performing simple protein-ligand site-specific docking using Pyrx. In this article, we are going to perform virtual screening using Pyrx. (more…)

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Docking

How to perform metal ion-protein docking using idock?

Dr. Muniba Faiza

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How to perform metal ion-protein docking using idock?

Previously, we provided a tutorial on the installation of idock on Ubuntu (Linux). In this article, we are going to demonstrate the docking of a metal ion (such as Zn, Mg, Fe, etc.,) with a protein using idock. (more…)

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Docking

How to install idock on Ubuntu?

Dr. Muniba Faiza

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How to install idock on Ubuntu?

idock [1] 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…)

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Docking

How to analyze HADDOCK results using Pymol script generated from PRODIGY?

Dr. Muniba Faiza

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In one of our previously published articles, we demonstrated protein-protein docking using HADDOCK2.4 [1]. In this article, we are going to demonstrate the HADDOCK results analysis using a Pymol script generated from the PRODIGY server [2]. (more…)

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Installing PatchDock on Ubuntu (Linux)

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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…)

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Protein-protein docking using HADDOCK2.4 web server

Dr. Muniba Faiza

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Protein-protein docking using HADDOCK2.4 web server

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