linux system Centos7 | Ubuntu system installs the molecular docking software AutoDockTools and implements molecular docking
1. Install AutoDockTools (MGLTools) on Linux
Follow the steps below to install AutoDockTools (MGLTools)
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Download the installation package, link (https://ccsb.scripps.edu/mgltools/downloads/), my Linux system is 64-bit, download the red mark, copy it to the Linux target folder (it is recommended to create a new one in the desktop or Home directory A folder for software packages).
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Shell terminal to install:
a. Enter the folder where the installation package is located via the terminal and obtain root permissions; grant the code installation permissions;
cd /home/... #Target folder, change according to the location of the target program file su #Get root permissions chmod 777 mgltools_Linux-x86_64_1.5.6_Install #Give code installation permissions ./mgltools_Linux-x86_64_1.5.6_Install #Install software
b. Run the installation:
./mgltools_Linux-x86_64_1.5.6_Install #Run the installation
c. Configure environment variables:
gedit ~/.bashrc #Configure environment variables or vi ~/.bashrc #Configure environment variables
After entering the above command in the terminal, an environment variable text dialog box will pop up. Add the following code at the end (enter i on the keyboard to enter editing mode), and change the path to the target folder of the software installation (note: this is not the location of the installation package) ):
export PATH=$PATH:/home/Carlos/MGLTools-1.5.6/bin #Write the bashrc file and save it
source ~/.bashrc #Refresh environment variables
d. The test is as follows:
adt #Run the program
It indicates that it can be opened normally and the installation is completed. If an error is reported, please see d.
e. The error reported may be that some necessary libraries or operating environments are missing. Just install according to the prompts. For example, my centos7.0 system lacks mesa-libGLU, so additional installation is required. Install it through the following command, and finally run adt again to succeed. .
su #Enter super command yum inatall mesa-libGLU #Install libGLU
2. Install AutoGrid and AutoDock packages on Linux
- Download the installation package, link (https://ccsb.scripps.edu/mgltools/downloads/Download AutoDock4 – AutoDockhttps://ccsb.scripps.edu/mgltools/downloads/), download the red mark, and copy it to the linux target folder .
2. Unzip the compressed package and use tar -xvf autodocksuite-4.2.6-x86_64Linux2.tar to get the folder containing autogrid4 and autodock4 files. Since the software has been compiled in advance, you can use it directly:
Each time you need to put the calculation file and the program in a folder, call it using the following method:
Call grid: ./autogrid4 -p xxx.gpf -l xxx.glg
Call dock: ./autodock4 -p xxx.gpf -l xxx.glg
However, for ease of use, it is strongly recommended to put them in the command root directory, that is, transfer them to the /usr/bin path. Every subsequent call can be made directly through:
(Calling grid: autogrid4 -p xxx.gpf -l xxx.glg
Call dock: autodock4 -p xxx.gpf -l xxx.glg)
tar -xvf autodocksuite-4.2.6-x86_64Linux2.tar #Extract cp /home/xxxxx/autogrid4 /usr/bin/autogrid4 #Transfer autogrid4 to the root directory of the execution command cp /home/xxxxx/autodock4 /usr/bin/autodock4 #Transfer autoduck4 to the root directory of the execution command
3. Molecular docking calculation details
- Prepare in advance:
a. Protein: Protein receptor. The world’s largest protein crystal structure database is the RCSB PDB database (RCSB PDB: Homepage). The PDB database is currently the most important database for collecting biological macromolecule structures. It is based on X-Ray single crystal diffraction. , NMR nuclear magnetic resonance, electron diffraction and other experimental methods to determine the three-dimensional structure database of proteins, polysaccharides, nucleic acids, viruses and other biological macromolecules. It is currently the most complete, authoritative and recognized crystal database in the world with structural information.
Here, we take the MYOSIN-9 protein as an example. The method to download the structure in pdb format is as follows:
b.ligand: Small ligand molecule. Here we take fullerene derivatives (typical derivatives of fullerene) as an example. You can also prepare a small molecule by yourself. My molecular coordinate information will not be provided here. At this point, the receptor molecules and ligand small molecules have been prepared.
c. Use PyMol software to process host molecules and receptor molecules. The latest version. PyMol is a simple-to-operate, powerful molecular and protein visualization software developed by Schr?dinger Company. Researchers can apply for the latest educational version from the official website. It is a very You can obtain the lic file (PyMOL | pymol.org) by simply applying. At the same time, the open source version of pymo (https://github.com/schrodinger/pymol-open-source) can be downloaded directly from the website, but the version is older. . Therefore, select the version to download based on your needs. Note: You also need to install python version 3.0 or above (Welcome to Python.org). Install it by yourself, just like ordinary software installation.
- Handling receptor molecules and ligand molecules
a. Receptor molecules
Here you can directly use Pymol to open the molecular structure file in pdb format that we downloaded. If it is a protein from the PDB database, you can also download it through the command fetch 4eto. 4eto is the PDB ID of the protein. After pressing Enter, you will see our protein structure in the visualization window.
After installation, first we open the pyMOL software:
Open the protein molecule through file→open. If you need to view the sequence of the protein, click S in the lower right corner of the software and it will come out. Or check Sequence from the menu bar Display to adjust the unreasonable structure and units of the protein. For example, remove water molecules, remove unnecessary oxygen atoms, remove water molecules, etc. Here we mainly remove excess oxygen atoms and water molecules (note: if there are Metal ions, or seemingly redundant inorganic ions, need to be removed according to the actual situation. If this part is a component of the protein, it cannot be removed.), select the oxygen atoms and water molecules that need to be removed on the sequence, right-click, and select remove. It can be removed, and the same applies to the others:
After processing, save it as a new pdb file: file→export molecule→save→name .pdb
Open the installed Autodocktools (MGTools), file→read molecule to read in the molecule, and then add hydrogen. Because the protein crystal structure downloaded from the pdb database does not have hydrogen atoms, so we need to add hydrogen atoms. This One step is necessary. Note that the hydrogenation here is full hydrogen.
Then:
Then save it as a receptor molecule, pdbqt file:
Then:
Then:
Delete molecules from the window for subsequent operations:
b. Ligand molecules
Ligand molecule (the default structure is already optimized. If it has not been optimized or has not been produced, you can first draw the three-dimensional structure of the ligand molecule through chemioffce, gaussview, chemdraw, etc. Then use quantitative calculation software such as Gauss, MS, VASP or even chembio3d performs structural optimization, and finally saves it as a file with the suffix .mol2 or .pdb). Here is an optimized small molecule coordinate, copy and paste it into the text, and modify the suffix to .pdb.
REMARK 1 File created by GaussView 5.0.8 HETATM 1 C 0 -0.868 0.131 0.851 C HETATM 2 C 0 0.509 0.131 0.851 C HETATM 3 C 0 1.034 1.463 0.851 C HETATM 4 C 0 0.028 2.404 0.852 C HETATM 5 S 0 -1.483 1.686 0.852 S HETATM 6 H 0 -1.503 -0.753 0.851 H HETATM 7 H 0 1.141 -0.759 0.851 H HETATM 8 H 0 2.104 1.683 0.851 H HETATM 9 C 0 0.225 3.931 0.853 C HETATM 10 C 0 -0.781 4.871 0.854 C HETATM 11 S 0 1.736 4.648 0.853 S HETATM 12 C 0 -0.256 6.203 0.855 C HETATM 13 H 0 -1.851 4.651 0.854 H HETATM 14 C 0 1.121 6.203 0.855 C HETATM 15 H 0 -0.888 7.093 0.857 H HETATM 16 H 0 1.756 7.087 0.855 H END CONECT 1 2 5 6 CONECT 2 1 3 7 CONECT 3 2 4 8 CONECT 4 3 5 9 CONECT 5 1 4 CONECT 6 1 CONECT 7 2 CONECT 8 3 CONECT 9 10 11 4 CONECT 10 9 12 13 CONECT 11 9 14 CONECT 12 10 14 15 CONECT 13 10 CONECT 14 12 11 16 CONECT 15 12 CONECT 16 14
Then load the molecule: file→read molecule→select the ligand molecule
Add root to the ligand molecule:
Click Ligand→input→choose→select molecules→ok
Click ligand→torsion tree→detect root: This step is for the software to automatically determine the root of the ligand.
Click ligand→torsion tree→choose torsion: This step is for the software to automatically determine the keys that can be twisted. Red indicates non-rotatable keys (cannot be changed manually), green indicates rotatable keys, and purple indicates non-rotatable keys. If you want to switch the keys, you can To rotate or not rotate, just hold down the shift key and click the corresponding key (the color will switch between green and purple), and click "done" when finished.
After rooting is completed, ligand→output→save it in pdbqt format! Exit or delete the current window molecule
c. Generate receptor network (Grid setup) and run
Import receptor: Grid→macromolecule→open→select protein molecule
Import ligands: Grid→set map types→open legand→select ligand molecules
Grid→Grid box (Before clicking, you need to move the ligand molecule outside the protein molecule. How to move: Click Dejavu GUI→root plus sign→select the ligand molecule. Click off the check mark in Perferences, right-click the mouse to move, and remove the check mark after completion. recover)
Grid box, adjust red, green and blue to make the box wrap the protein, click spacing to zoom in and out: According to experience or literature reports, interacting groups or active sites are the objects of investigation, and the set box needs to include them. If it is unknown, the egg white can be completely wrapped.
Save box parameters: File→close saving current
Grid→output→Output and save in GPF format
The following two systems (windows and linux) can run AutoGrid, you only need to use one of them:
Windows (the running precursor is to install the autogrid software on the windows system. If it is not installed, please install it yourself):
Run Grid: run→autogrid→click the third path again to open the gpf format file, where the glg format file will be automatically generated on the fourth line→set the nice level to 20→click launch
A small window will pop up here, indicating that the calculation is in progress and wait for the completion of the small window.
Linux:
Import the four files in the figure below. The red box corresponds to the processed protein receptor molecule and the gpf file generated above. The green box corresponds to the autogrid4 and autodock4 software used for this calculation (see 2.1 for the installation method).
Enter the command “./autogrid4 -p MYOSIN-9.gpf -l Grid.glg & amp;” in the Linux terminal.
Autogrid4 starts running in the background until it ends, outputting multiple suffix .map files and a Grid.glg file.
d. Generate molecular docking file and run
Docking→macromolecule→set rigid filename→selectin receptor molecule (here, the protein molecule is set to a rigid molecule)
Docking→ligand→open→click ligand→accept
Docking→ligand→choose→click the second→select→accept
Docking→search parameters→genetic algorithm→accept
Docking→docking parameters→accept
Docking→output→lamarkian GA(4.2)→Save in dpf format
The following two systems (windows and linux) can run AutoDuck, you only need to use one of them:
Windows:
Run→autodock→Next, do the same as autogrid! Wait for it to end and see the result
Clear after the calculation is completed, edit→delet→delete all molecules
Linux:
Import the suffix .dpf file into the same folder of the Linux system as the calculation grid. Be careful to import the ligand molecules at the same time.
Enter the command "./autodock4 -p MYOSIN-9.dpf -l Dock.dlg & amp;" in the Linux terminal. After the operation is completed, a Dock.dlg file will be generated, which is the final output file.
e. Final result analysis
The Dock.dlg file will be obtained after running.
Click Analyze→docking→open→dlg format file
Analyze→Import receptor molecule macromolecule→open
Analyze→conformations→load (a lot of data comes out, mainly looking at the binding energy, generally choose the first one with the lowest energy). You can also view the specific position of each conformation through play.
Different positions show different binding energies, choose the best one to save:
Write complex, save it in pdbqt format, and can be further beautified through visualization software such as pymol.
That’s it! ! ! The above process is relatively detailed in operation, and some operations are shown in pictures. Although some operations are only textual descriptions, they are all process-based operations corresponding to the menu bar. It is relatively easy to complete the operations in the order of the arrows, so there is no need to go into details. It is recommended that students who are engaged in quantitative calculations install a virtual machine on a Windows computer and install a Linux system on the virtual machine. This is very helpful for testing quantitative software and learning Linux knowledge. If conditions permit, you can install a separate Linux system. Computers are also acceptable, but try not to modify and install software you don’t understand or change environment configurations on public platforms.
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