¶ Introduction
In this usecase, we will show you how to analyze the binding site of tubulin protein to identify region to grow the hit compound.
¶ Use case
¶ Reference pocket selection
- Type 5S4O in the text search and click Enter
- Click on the button “Open” on the right-hand side to open the structure in the Workspace
- Click on Pocket Browser in the dropdown menu
- Click on pocket number 3 with ligand O0J
¶ Pocket visualization
- Click on “Cartoon representation option” and hide cartoon
- Click on “Water representation option” and show Water molecules
- Click on “Interaction representation option” and toggle on water-mediated interaction in the Polar group
- Click on “Surface representation options” and:
- Add ligand solid “High quality molecular surface”, and set opacity 0,5
- Add pocket mesh “High quality molecular surface”
The visualization is clearer now to see that there is space in the pocket to grow the ligand and displace water molecules.
- Measure distances between sulfur of the ligand and the three nearby water molecules (waters 752, 788, 794)
¶ Structures overlay
- Go back to the Workspace navigation page and click on “ADD STRUCTURES” on the top left hand-side. Then click “From Code” and type the PDB: 5S5K, toggle on “loaded session” and click “add” to add the structure to the temporary structure collection
- Click on the eye button next to 5S5K to superpose the structure
Look how the phenyl is fitting well in the subpocket which in structure 5S4O is filled by water molecules.
- Open the structure from code 5SB7 to see the final compound todalam that contains a moiety filing the water pocket.
