Protein-protein docking can be computationally intensive, especially when the search space is left unconstrained. If you know or suspect where a protein binding site lies, one practical way to speed up protein docking is by limiting the search domain. In this post, we explore how to restrict the angular search domain within the Hex Extension in SAMSON.
Why restricting the search domain helps
Hex performs protein docking using spherical coordinate sampling, where it rotates the ligand around the receptor across a range of angles. By default, both the receptor and ligand may rotate up to 180°, effectively scanning the full sphere. But if you already have a rough idea of the binding site location, you can limit these ranges, reducing both search time and the number of irrelevant results.
For instance, by reducing the angle from 180° to 45°, Hex only samples rotations within a conical region—significantly narrowing the docking possibilities.
Step-by-step: Defining range angles
1. In SAMSON, open the Hex application from Home > Apps > Biology > Hex.
2. Assign one protein as the receptor and the other as the ligand. (For example, 2PTC_E as receptor and 2PTC_I as ligand.)
3. Make sure that the Sampling method is set to Range angles.
4. Click Advanced parameters to access the range settings.
5. In the Receptor angle range and Ligand angle range fields, input smaller values like 45°.
When set up correctly, two cones should appear visually in the 3D view—one on each protein—with their apexes connected by an axis representing the docking path. These cones show the allowable orientation ranges for the receptor and ligand molecules during docking.
When and why to use restricted range angles
This approach is useful when:
- You already know the binding site location from experimental data or previous studies.
- You want to prioritize speed by avoiding blind docking over the entire surface.
- You aim to reduce the number of irrelevant docking solutions.
Additionally, you can limit the twist angle—the ligand’s rotation around the intermolecular axis—if rotational flexibility is known to be constrained in the binding event.
Fine-tuning your protein orientations
Before defining the range angles, you may want to preposition the ligand near the suspected binding site. SAMSON’s Move editors allow you to translate and rotate molecules interactively—ensuring the cones focus precisely on relevant areas.
By combining informed orientation and restricted angle ranges, docking becomes faster and potentially more accurate by reducing noise in the search results.
To learn more about the full workflow, visit the full Hex Docking documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.