One common pain point in molecular modeling is accurately and efficiently defining the binding site for docking studies. Reproducibility, speed, and the likelihood of successful docking all rely on this small but critical step. Fortunately, for users of the FITTED Suite Extension for SAMSON, there’s a quick and consistent approach available—especially if you’re working from crystal structures or doing self-docking.
In this post, we’ll walk through how to define a binding site in just a few clicks using a bound ligand in SAMSON’s FITTED Suite. This is particularly useful for self-docking, validation studies, or when your binding pose is known from experimental data.
Why this matters
Incorrect binding site definition can lead to poor docking results and wasted computing time. Many tools require you to manually center grids, adjust box dimensions, or estimate active site coordinates. The FITTED Suite helps reduce this guesswork by allowing direct selection based on present ligands.
Step-by-step: Defining the binding site
Let’s take the 1E2K protein-ligand complex as an example. This structure includes a bound ligand (TMC 500) in thymidine kinase, which we can use to define the docking region.
1. Locate the bound ligand
Use the Document view in SAMSON to search for “TMC 500.” Double-click on the TMC 500 group or expand Chain A to find it.
2. Set the binding site from the ligand
Once selected, go to the FITTED Suite panel in the app, navigate to the “Define binding site” section, and select From bound ligand. Click the Set button.
This tells the program to automatically compute the center and radius of the search grid based on the coordinates of the ligand—eliminating the need to define these manually. 🧭
3. (Optional) Customize position or use selection
If you don’t have a bound ligand, you can use one of two alternative methods:
- From selection: Select atoms in the receptor and define the centroid manually.
- From position: Place and adjust a sphere in the 3D viewport to define the center of the docking region.
These options give flexibility for blind docking or for exploring novel binding areas.
Why use bound ligands when available?
If you’re aiming for reproducible results, consistent benchmarking, or want to validate a docking protocol (e.g., redocking), using a known binding pose helps control the variables. In this context, the “From bound ligand” approach is especially efficient.
Visual confirmation
You can confirm your binding site selection using the Viewport. The grid or region for the search will appear around the selected ligand position. This ensures the setup is correctly configured before proceeding with docking runs.
Conclusion
Defining the binding site doesn’t need to involve manual coordinate input or time-consuming grid setup. If you’re starting from a crystal structure or reference ligand, FITTED Suite for SAMSON makes it as easy as selecting the ligand and clicking a button.
To learn more about docking workflows using the FITTED Suite in SAMSON, visit the full documentation at this link.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net