One common challenge in protein-protein docking is the overwhelming number of possible orientations to explore. Each additional degree of rotational freedom can substantially increase docking time and the likelihood of false positives. Fortunately, you can reduce these issues by constraining the docking search area using range angles in the Hex Extension of SAMSON.
In this post, we’ll walk through why and how narrowing the search domain using angle constraints can speed up your docking calculations and boost meaningful results. If you’re already familiar with docking workflows and want more control over search performance, this technique might save you time—and improve accuracy.
Why use range angles?
By default, Hex evaluates protein docking orientations assuming a full 180° rotational freedom around the reference axis. This exhaustive sampling ensures coverage, but it’s often unnecessary—especially when you already know the rough location of the binding site.
Range angles let you define spherical cones around the receptor and ligand, guiding Hex to only search within these regions. This not only reduces the computational load, but may also lower the number of biologically implausible orientations in your results.
How to set range angles in Hex
Once you’ve loaded your protein structures into SAMSON and opened the Hex Extension (via Home > Apps > Biology > Hex), follow these steps:
- Set your receptor and ligand using the Set buttons after selecting the appropriate molecules in the Document view.
- Ensure the Sampling method is set to Range angles.
- Click Advanced parameters to access angle settings.
- Set the Receptor angle range and the Ligand angle range to a smaller value like 45°.
If the proteins are roughly aligned at the interaction zone, limiting the rotation to 45° around their respective centers often yields sufficient conformational flexibility without excessive exploration. You can also restrict the twist angle range if you want to limit torsional rotation about the axis connecting the centers of the two molecules.
This kind of setup results in two visual cones in the workspace:
The image shows the cone-shaped regions used to limit the docking orientations—an intuitive preview of the search space that helps keep your calculations focused.
When to use this approach
Range angle constraints work especially well for:
- Docking high-resolution crystal structures where minimal conformational change is expected.
- Reducing computational effort when dealing with multiple docking runs or libraries.
- Improving accuracy by guiding Hex focus around known interaction interfaces.
Keep in mind that if you’re unsure about the binding site, broader angles or default settings may be more appropriate. But when you do have prior information, don’t leave it unused—feed it into the docking strategy.
Conclusion
Using range angles in Hex allows you to focus the docking search domain, improving efficiency and relevance. It’s a small parameter tweak with significant benefits if applied thoughtfully. You retain visual feedback, full control, and can still modify other docking parameters as needed.
To learn more about search domain configuration and other advanced docking techniques, visit the full tutorial at this page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.