Preparation of small molecule ligands: There are many methods. You can use chemdraw to draw the small molecule structure and save it in mol format. Then open the mol format file with chem3D and save it as a pdb file.
Preparation of macromolecular receptors: You can download the pdb structure on the rcsb website. The proteins have different sources, such as plant sources or microbial sources. Just download them according to your needs.
In addition, the macromolecular receptors generally downloaded from the website contain solvents and small molecules of the original ligand, which need to be deleted. The method I use is to open the protein receptor with pymol and execute two commands: remove solvent and remove organic (Remove small molecules).
1. Open the macromolecule: file-read molecule, open the prepared protein pdb file
2. Hydrogenation: is to add hydrogen atoms to the receptor protein, edit-hydrogens-add
3. Calculate charge: edit-charges-compute gaseigter, this step is to adjust all charges to integers
4. Set the atom type: edit-atoms-assign AD4 type
5. Output pdbqt file: file-save-write pdbqt, remember to manually add pdbqt suffix when naming, the following gpf, dpf files are also the same.
1. Open the small molecule: ligand-input-open
2. Adjust charge: edit-charges-check totals on residues, if a dialog box pops up, click spread charge and then click dismiss
3. Determine root, ligand-torsion-choose torsion, and then click done
4. Output pdbqt file, ligand-output-save as pdbqt
1. Open the pdbqt file of the macromolecule, grid-macromolecule-open
2. Open the pdbqt file of the small molecule, grid-set map types-open ligand
3. Set the grid range, grid-grid box, the upper red, green and blue adjust the length of the box in the three directions of xyz, and the lower red, green and blue adjust the center position of the box. After adjustment, remember to click file-close on the option box saving current
4. Output gpf file, grid-output-saving gpf
5. When running autogrid, run-run autogrid, and downloading and installing a series of autodock files, there will be two separate programs autogrid and autodock. Remember to download and save. This step uses the autogrid program. After selecting the corresponding file and program, click launch, it will run for a while, wait for the dialog box to disappear and get the glg file.
1. Docking-macromolecule-set rigid filename, set the rigid file name, so it is normal that the pdpqt file of macromolecules is not opened
2. Docking-ligand-open, open the pdpqt file of small molecules
3. Docking-search parameters-choose algorithms, each has its own advantages and disadvantages, I generally choose genetic algorithms
4. Docking-docking parameters
5. Docking-output- corresponds to step 3 to get the dpf file
6. Run autodock, run-run autodock, select the corresponding file and program (autodock program), click launch, it will run for a long time, wait for the dialog box to disappear and get the dlg file
1. Analyze-docking-open, open the dlg file, small molecules will appear on the interface
2. Analyze-macromolecule-open, open the pdbqt file of the macromolecule
3. analyze-conformations-play ranked by energy
4. The result will come out. You can click the penultimate button in the dialog box to set the content that can be viewed. Generally, binding energy and hydrogen bond are used as the inspection indicators.
5. Click analyze-glustering-show to see the intuitive binding energy distribution map.