Defining the binding site in protein-ligand docking is one of the most crucial — and sometimes tedious — steps in early-stage molecular modeling. If you’re working with a protein structure that already includes a bound ligand, you might wonder why you’re still setting up binding boxes manually or estimating grid centers by eye.
Fortunately, the FITTED Suite extension for SAMSON includes a simple but time-saving feature for this case: defining the binding site directly from the bound ligand. This approach is especially useful when performing self-docking, benchmarking docking accuracy, or preparing for covalent docking where the ligand’s position is already known.
Why it matters
Manual selection of a binding site — even with visualization tools — can introduce reproducibility issues or inconsistencies, particularly when different users define different centers or box sizes. By anchoring the site definition to an existing ligand, such variability is minimized, and users get consistent results faster.
How it works
In the FITTED Suite interface inside SAMSON, under the Define binding site section, you can select:
- From bound ligand
This feature lets you use the coordinates of an already-bound ligand as the center of the docking grid, automatically adjusting it to the appropriate radius and location.
In the 1E2K self-docking tutorial, users define the binding site based on the TMC 500 ligand:
After selecting the ligand in the Document view (e.g., by typing TMC 500 in the search bar), users simply click the Set button in the From bound ligand section.
That’s it — no manual grid creation required.
When to use it
This method is ideal in the following scenarios:
- Self-docking for benchmarking scoring functions or pose prediction accuracy
- Covalent inhibitor docking, where the ligand binds in a highly specific pose
- Virtual screening preparations when the reference structure includes a co-crystallized ligand
Alternative methods
If your structure does not include a bound ligand, the FITTED Suite still offers two other ways to define a binding site:
- From selection: select atoms and the docking box is centered on their centroid
- From position: manually place a sphere inside the viewport to define the center
While flexible, these alternatives can be more subjective and time-consuming, especially for less-experienced users.
Takeaway
If you’re working with a structure that already has a bound ligand, use it to streamline your docking preparation. You’ll save time, increase reproducibility, and reduce common pitfalls in binding site selection.
Learn more about the FITTED Suite and explore additional workflows like covalent docking or interaction analysis.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.