One of the common pain points in protein-protein docking is long computation times combined with a high number of false positives, especially when working with high-resolution structures. What if there were a simple strategy to significantly reduce search time and improve docking accuracy?
In this post, we’ll look at how to focus the docking search in the Hex Extension for SAMSON, by narrowing the search domain using what Hex calls range angles. This is particularly helpful when prior knowledge about the binding site is available—or when you at least know which regions of your proteins are likely to interact.
Why limit the search domain?
By default, Hex performs a spherical docking search, exploring a very wide range of protein orientations. This increases the chance of identifying the correct binding mode if nothing is known. But when we have some starting hypothesis, like known interface residues or structural alignment, constraining the search domain can:
- Reduce the number of incorrect predictions
- Speed up docking computation significantly
- Help focus energy minimizations on relevant solutions
How to configure range angles in SAMSON
After setting up your system and launching the Hex app via Home > Apps > Biology > Hex, click on Advanced parameters to access search domain settings.
Set the Sampling method to Range angles. You will then be able to define separate angular constraints for both the receptor and the ligand. These define cones of allowed orientations around an axis linking the centers of both proteins.
For example, you could set:
- Receptor angle range: 45°
- Ligand angle range: 45°
This means that only poses where proteins stay within these cones are explored during docking.
When does this help?
This technique is particularly useful when:
- You’ve manually aligned the two proteins in a likely-bound state
- You know the functional interface from other sources (e.g. literature)
- You want faster computations and fewer false positives
By reducing angular freedom, Hex filters out thousands of unlikely orientations upfront, giving the docking algorithm a head start toward biologically relevant configurations.
Bonus: twisting parameters
You can also constrain the twist angle, i.e. the rotational degree about the axis connecting the protein centers. If one orientation is clearly preferred, locking the twist can further reduce ambiguity. But leave some flexibility if in doubt.
Conclusion
Search domain restriction in Hex is an intuitive yet powerful way to improve docking reliability. It won’t replace biological insight—but it can help you translate that insight into tighter and faster searches.
To learn more about using Hex for protein docking in SAMSON, check out the complete documentation here: https://documentation.samson-connect.net/tutorials/hex/protein-docking-with-hex/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON here.