One of the most common pain points for molecular modelers performing protein-protein docking is the time it takes to get meaningful results. Exhaustive searches across all possible orientations are computationally intensive, especially when docking larger biomolecules.
If you’ve found yourself waiting too long for docking results—or getting too many irrelevant ones—you’ll be glad to know that limiting the search domain using the Hex Extension in SAMSON can drastically reduce computation time while increasing relevance.
Why limit the search domain?
By default, docking algorithms may explore the full 360° rotational space for both receptor and ligand molecules. If you already have knowledge about likely binding sites or orientations (e.g. from literature, experimental data, or homologous structures), you can restrict the angular search space and avoid wasting time on biologically implausible interactions.
How to do this in SAMSON with Hex
Once your receptor and ligand are prepared and loaded into SAMSON:
- Launch the Hex extension via Home > Apps > Biology > Hex.
- Assign your receptor and ligand (e.g.
2PTC_Eas receptor and2PTC_Ias ligand). - In the Hex interface, set the Sampling method to Range angles.
- Click on Advanced parameters to fine-tune angular restrictions.
Range angles explained
In Hex, range angles define spherical cones centered on the axis running between the centers of two molecules. These cones limit how far around the receptor the ligand’s search is permitted to go.
For example, setting both the receptor and ligand rotation angles to 45° restricts the search domain to a narrow region around their initial orientation.
If you roughly position the ligand near the binding site beforehand (using tools like the Move editor), these 45° cones offer an efficient balance—tight enough to reduce irrelevant solutions but flexible enough to discover binding conformations close to the initial pose.
What about the twist angle?
The ligand can also be rotated (twisted) around the receptor-ligand axis. You can narrow this down, too—especially useful if the interface geometry is known. Restricting the Twist angle helps focus on meaningful rotations and speeds things up even more.
When to use this approach
- You have prior knowledge of binding interfaces
- You’re docking multiple ligands and want to speed up batch processes
- You’re doing iterative refinement of docking results using other filters after a coarse sweep
Good to know:
Even if you’re unsure of exact binding sites, you can still orient the molecules intuitively and use larger range angles—say 90° to 120°—to speed up the search without overly narrowing the possibilities.
Proper use of range angles is a powerful way to combine domain knowledge with efficient computation. In practice, this can cut docking times from many minutes to just a few, and significantly reduce irrelevant results cluttering your post-processing phase.
To learn how to fully configure this feature in SAMSON, consult the official tutorial: Protein Docking with Hex.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.