One common challenge when performing protein-protein docking is the high number of docking solutions that turn out to be incorrect upon detailed inspection. Especially when the potential binding site is already known, a full-sphere unconstrained search wastes time and resources, generating many false positives that confuse rather than clarify.
Fortunately, the Hex Extension in SAMSON offers a powerful way to reduce the number of irrelevant docking solutions: use Range angles to narrow the search space during docking.
Why Range Angles Matter
Typical docking searches involve rotating one protein (the ligand) around the other (the receptor) to explore possible binding orientations. Without any restriction, the search explores all 360 degrees of potential ligand orientations. This is useful when little is known about the binding site, but inefficient—and often misleading—when prior knowledge about the interaction interface exists.
Using Range angles, you can define conical regions on the receptor and ligand that limit the orientations considered during docking. These cones restrict the accessible orientation space to within a specified angular range, significantly reducing false positives and speeding up computations. It’s a particularly practical approach when working with high-resolution crystal structures.
How to Apply Range Angles in SAMSON
- In the Hex app (accessible via Home > Apps > Biology > Hex), set your receptor and ligand. For this tutorial example, use 2PTC_E as the receptor and 2PTC_I as the ligand.
- Scroll down the Hex interface and set the Sampling method to Range angles.
- Open Advanced parameters and define the Receptor angle range and the Ligand angle range. A value of 45 degrees is generally a sensible choice—restrictive enough to reduce noise, flexible enough to capture variations.
- Two cone visualizations will appear in the 3D view, indicating the spatial constraints applied. These cones originate from the centers of the receptor and ligand and restrict rotational sampling to their volumes.
- You can also specify a Twist angle range for the ligand, further controlling its rotation about the intermolecular axis.
Pro Tips
- If you know the orientation of the binding interface, manually align the ligand beforehand using the Move editors.
- Use narrower angle ranges for more precise docking when the binding site is well-known.
- Visualize the range cones before launching the docking run to verify that you’re targeting the correct interface area.
Better Results, Faster
Using Range angles is not mandatory, but it is often the key to shifting from exploratory to targeted docking. It helps focus computational effort, shortens processing time, and results in fewer incorrect predictions—especially useful in high-throughput docking sessions or workflows involving known interface residues.
To learn more about additional Hex parameters or the full docking workflow in SAMSON, visit the official step-by-step tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.