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Copyright License

Copyright (c) 2020 Shoab Saadat [dr.shoaibsaadat@gmail.com]

Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.

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Help File

I explain the steps to follow in order to get the docking pipeline flowing:

1. Get yourself a linux system with python3 installed

sudo apt update
sudo apt upgrade
sudo apt install python3
sudo apt install python3-pip

2. Prepare the linux system using my python-tool

Make sure you have autodock_python.py in the current folder

python3 autodock_python.py -s all

3. Download typical directory structure for docking

It creates a directory named Vina_Project and takes you in it.

python3 autodock_python.py -d all

4. Search Chembl Database

You can search the Chembl database for selection of ligands from within command prompt

python3 autodock_python.py -sc

5. Prepare protein receptor

Now you will be in Vina_Project folder, here, put your receptor_xyz.pdb file in receptor folder to start.

python3 autodock_python.py -pp [receptor_name] / ["all"]

It offers two options for ligand processing.It is a powerful protein preparation app which uses one of the following two systems for subsequent processing based on the availability on your system and your choice:

• Using Pymol with openbabel In this case, it uses pymol to remove water molecules and add polar hydrogen while using openbabel for the charge addition and pdbqt conversion.
• Using MGLTools and Audodock Tools This is an advanced conversion tool. It automatically removes water, adds hydrogen, merges nonpolar hydrogen charges, merges lone-pairs, remove chains composed entirely of residues of types other than the standard 20 amino acids, and adds gasteiger charges to the peptide molecule.

Once you select an option, will be asked to select a number of chains to keep from your protein molecule. You can opt to keep all the chains. It then proceeds to prepare your receptor.

6. Create PDBQTs from all ligands

It offers two options for ligand processing.

• Using Open babel
• Using Autodock Tools It automatically removes water, adds hydrogen, merges nonpolar hydrogen charges and merges lone-pairs. before using it, make sure you have sdf files in ligands_sdfs folder.

python3 autodock_python.py -p all

7. Create a grid file for search box

Using this command, you can provide residue numbers of the most important amino acids in your receptor protein and it will create a search box grid file around those receptors. Residues can be based on the literature study or fetched from pocket analyzing softwares, such as, CASTp, PASS, Pocket-Finder, PocketPicker etc. When asked, residue numbers should be entered as seperated by space like "6 12 50".

python3 autodock_python.py -g [receptor_name] / ["all"]

This will create a text file with a prefix of "grid_" in the main app directory. This file will be later used automatically for the subsequent docking step.

Now you should have the following files:

• ./vina
• ./vina_split
• ./receptor/receptor_xyz.pdbqt (Keep the pdb file in this folder as well even if you make a pdbqt)
• ./ligands_sdfs/xyz.sdfs (Put your drug sdfs here)
• ./grid.txt (you can make from autodock tools by simply saving the gridbox output as txt or use the tool above to autogenerate if you know the key residue numbers to make the box around)
• ./res (resources folder)
• ./ligands_pdbqt/ (should have been populated in an earlier step)

8. Start the AutoDock process

It does it for any pdbqt receptor in receptor folder and all ligand pdbqts in ligands_pdbqts folder

python3 autodock_python.py -ad [receptor_name] / ["all"]

9. Create result files

It creates a results file for each receptor with finalized info

python3 autodock_python.py -r [receptor_name] / ["all"]

10. Make lookup drug table files

It creates three kinds of drugtables to compare results with actual ligand details

python3 autodock_python.py -dt [receptor_name] / ["all"]

Note: With each command, you can use all or a certain receptor name. At any time if you want to know the receptor names for more targetted commands, type python3 autodock_python.py -i