One common challenge in protein-protein docking is the overwhelming number of false positives generated during the search phase. These incorrect poses can significantly slow down interpretation and reduce confidence in your results. A practical strategy to minimize this issue is to limit the search domain using angle constraints in Hex, right from the Hex Extension in SAMSON.
The Hex docking algorithm operates in spherical coordinates and, by default, explores a full 180° around both proteins—receptor and ligand. This exhaustive search maximizes coverage, but often at the cost of increasing irrelevant docking results, especially when prior biological knowledge is available. Narrowing the search through angle constraints can help focus computing resources on biologically plausible conformations.
Why limit the angular search?
- Fewer false positives and more meaningful results.
- Improved docking times by narrowing the search space.
- Better performance when binding interfaces are partially known.
How to set up constrained angular search in SAMSON
First, set the sampling method in the Hex interface to Range angles. Then, enter the Advanced parameters section to configure specific rotational ranges.
Here’s the key idea: instead of allowing the docking to explore every possible angle, you define cones of exploration (Range angles), centered along the intermolecular axis connecting the receptor and ligand. The smaller the cone, the more focused the search.
A Range angle of 180° means no constraint—Hex explores the entire 3D space around the molecule. However, if you already have an approximate idea of the binding site, you can:
- Visually orient the ligand close to the receptor’s surface using SAMSON’s move tools.
- Then set both receptor and ligand range angles to something smaller (e.g.,
45°) to rigorously restrict Hex’s rotational search to a biologically plausible region.
This creates cones that segment the docking space and dramatically improve predictive quality, especially when docking based on secondary structure interfaces or known partial structures.
Setting the twist angle
In addition to range angles, you can also limit the twist angle, corresponding to a rotation around the axis connecting the two molecules. This is helpful if binding involves specific symmetry or if certain rotational poses are known to be unfavorable.
When should you apply this strategy?
- When you’ve derived information from mutational analysis, cryo-EM envelopes, or cross-linking data suggesting a specific interaction interface.
- When docking structurally rigid domains, where major conformational shifts are unlikely.
- When running high-throughput docking and need quick reduction of spurious poses.
The best part? By physically visualizing and adjusting these angular constraints directly in SAMSON, you gain intuitive, real-time control over your molecular modeling workflow—no scripting or manual file editing necessary.
To learn more about the full docking workflow in SAMSON and how to use Hex effectively, visit the full tutorial documentation: Protein docking with Hex in SAMSON.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.