One of the most common challenges in protein-protein docking is managing the enormous search space—which often results in high computational costs and a surplus of false positives. If you know the likely binding region in advance, there’s a simple way to significantly reduce both processing time and irrelevant results: constraining the docking search domain using range angles in Hex for SAMSON.
This feature is particularly helpful when you want more precision without losing flexibility entirely.
Why limit the docking search domain?
By default, a docking search in Hex explores all possible orientations of the ligand relative to the receptor. While that’s great if you have no idea where docking might happen, it’s overkill if you already know—or can estimate—the binding site location.
Limiting the angular range of motion helps steer the search engine toward meaningful conformations by constraining the directions in which Hex samples orientations.
How to use Range Angles in SAMSON
Once you’re in the Hex Extension within SAMSON, follow these steps:
- Set the Sampling method to Range angles.
- Click on Advanced parameters to access the range angle controls.
- Adjust the Receptor angle range and Ligand angle range.
For instance, if you already placed the ligand close to the binding site with basic spatial knowledge of the complex, using values like 45° for both ranges can be highly effective.
Visually, Hex shows two cones extending from the centers of the ligand and receptor towards one another. These cones represent the domain within which Hex will consider possible docking orientations—any orientation outside these cones is ignored by the search algorithm.
Saving compute time and improving accuracy
By limiting the space to explore, you reduce distractions for the docking engine—and your compute resources. Just as importantly, you avoid meaningless poses by directing the search only where it matters. This trade-off between flexibility and focus often results in more realistic docking results with less noise.
Quick steps for practical setup
- Move and orient the ligand manually near the known or suspected binding site (you can use Move editors for precision).
- Then set angular constraints: 45° is typically enough for a targeted but not overly strict search.
- If potential conformational changes are minimal, this strategy works especially well with crystal structures.
In more flexible systems, you might want to loosen these constraints slightly or run multiple searches with different parameter sets. But if the binding interface is relatively certain, limiting range angles is a reliable way to focus your efforts.
Learn more in the full documentation: https://documentation.samson-connect.net/tutorials/hex/protein-docking-with-hex/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.