One of the most common challenges in protein-protein docking is the trade-off between accuracy and computational time. A full rotational search in docking can be very intensive, especially when you’re screening multiple systems or tweaking parameters. Fortunately, if you already have some structural knowledge, you can drastically reduce docking time by limiting the search domain. Let’s take a look at how to efficiently restrict the docking search space using the Range Angles in the Hex Extension within SAMSON.
The docking process in Hex is done in spherical coordinates. By default, it assumes no prior knowledge of the protein-protein interaction interface, and thus explores a full range of angular orientations (180 degrees per structure), which may lead to long search times. But what if you already know (or suspect) where the binding sites are located?
Why limit the search domain?
Let’s say you have a ligand already positioned near a receptor’s binding site. You can then significantly constrain the angular rotation domain around the binding axis (called the intermolecular axis), so that Hex focuses only on relevant orientations. This does not just save time — it can actually improve result quality by preventing irrelevant modes from cluttering the top-ranked results.
How to adjust Range Angles
To apply this strategy:
- Set the Sampling method to Range angles.
- Click on Advanced parameters.
- Adjust the Receptor angle range and the Ligand angle range. For example, setting both values to
45degrees limits the search space to a cone-shaped domain, centered on each protein.
In the image above, two cones are visualized – one for the receptor and one for the ligand – showing the limited angular regions considered during the docking search.
Positioning and alignment tips
Before defining the range angles, it helps if the ligand is roughly positioned near (and pointing toward) the receptor’s binding site. You can manually align them using the Move editors in SAMSON. Then, a smaller range angle constraint like 45° ensures only local refinements are explored.
Twist angle control
You can also manage the Twist angle range, which controls the rotation of the ligand around the intermolecular axis itself. This gives you fine control over the orientation variability allowed during docking.
By applying these constraints, SAMSON’s Hex Extension becomes much more efficient for typical structure-guided docking scenarios where the approximate interface is known. It’s a small tweak that can save a lot of time ⏱️.
To learn more about the setup and other Hex parameters, you can read the full tutorial in the SAMSON documentation: Protein docking with Hex
*Note: SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.