4.2.2.2 Docking a similar ligand

This procedure is used when a structure of a complex with a ligand similar to that of your interest is available. In this case, we chose as a study case the lipid kinase Vps34 (PDB ID: 4UWL). This ligand is similar to that of 4UWH, so we can use it as receptor.

Receptor (4uwh.pdb) and ligand (ligand.pdb) files are available at Installation_path/Doc/Tutorials/I_Simple_Docking/Box_Hetero/2.2.Similar_Ligand folder. The crystal structure of the complex (complex.pdb) is available as well for comparison purposes.

1. Open AMDock program or just create a new project if you are at “Results Analysis” tab
2. Select Autodock Vina
3. Set the Project Name (default Docking_Project)
4. Set the Location for Project and push the button “Create Project”
5. Check that “Simple Docking” checkbox is selected (It is checked by default)
6. Choose the receptor file (Installation_path/Doc/Tutorials/I_Simple_Docking/Box_Hetero/2.2.Similar_Ligand/4uwh.pdb)
7. Choose the ligand file (Installation_path/Doc/Tutorials/I_Simple_Docking/ Box_Hetero/2.2.Similar_Ligand /ligand.pdb)

Before going to the next step, go to the configuration tab and check “Ligand Protonation” with OpenBabel

8. Press the “Prepare Input” button
9. Then, for defining a search space, pick “Center on Hetero” and select the ligand “A:JXM:1876”
10. Press “Define Search Space” button

Once the search space is defined, you can see the box in the receptor by pressing the button “Show in PyMOL”(Showed in Figure 8)

Note: If you want to modify the box, you can use the AMDdock plugin in PyMOL. More details about this procedure here.

11. Press the “Run” button

12. When docking run ends, the “Results Analysis” tab will appear automatically. There, you will observe a summarizing table with Binding Energies, Estimated Ki values, and Ligand Efficiencies. The number of poses and energies can vary since this is docking engine dependent.

13. In the results table, just the first pose is selected. Press the button “Show in PyMOL” in the bottom left corner to visualize the complex.

If you want to see all the predicted poses, just select all the poses in the result table and press “Show in PyMOL”

14. The crystal structure can be superposed on the predicted structure. Press “Open” in the upper left corner in PyMOL and find the X-ray structure (Installation_path/Doc/Tutorials/I_Simple_Docking/Box_Hetero/2.2.Similar_Ligand/complex.pdb)

15. A detailed report of the entire process can be seen on the right side of the screen, which allows for tracking all the results from different programs and algorithms. This log file can be saved in case an error occurred and sent to the developers.