One of the common issues faced by molecular modelers during protein-protein docking is the generation of too many false positives. These can make the analysis harder and drastically increase the time it takes to extract meaningful biological insights. A key technique to mitigate this is constraining the search domain using range angles in the Hex Extension in SAMSON.
This approach helps limit the orientation space explored during docking, focusing the search on the most relevant interaction zones between the ligand and the receptor. If done well, it significantly improves both result quality and computational efficiency.
Why Range Angles Matter
By default, Hex performs a full rotational docking search, where the ligand is allowed to explore all 360° orientations around the receptor. While thorough, this leads to an expansive search space and an abundance of low-quality candidate conformations.
If you already know or suspect the region of interest — say, a binding site from prior experimental data or literature — you can manually align the ligand near that interface and set up range angle constraints to limit the explored space. This helps reduce noise, improves docking precision, and saves compute time. 🎯
How to Set Up Range Angles in SAMSON
First, ensure that the Sampling method in the Hex interface is set to Range angles. Then, click on Advanced parameters to configure your angular constraints.
Here’s what each parameter does:
- Receptor angle range: Defines a spherical cone originating from the receptor’s center. Only orientations within this cone are explored. A smaller angle (e.g., 45°) narrows the focus.
- Ligand angle range: Similarly defines a cone from the ligand center. Again, smaller values zero in on a likely binding orientation.
- Twist angle range: Restricts the ligand’s rotation around the axis connecting the centers of the two proteins.
After configuring these ranges, Hex will visualize the constraints as cones, helping you fine-tune them by eye:
Tips to Get the Most Out of This Feature
- Use the Move editors to manually orient the ligand close to the suspected binding site before defining range angles.
- If you’re unsure about binding location, try a semi-restrained approach with moderate angles (e.g., 90°) for initial runs.
- Reduce range angles progressively across runs as you become more confident in the interaction region.
This targeted approach to docking not only reduces computation time but also improves overall prediction relevance by focusing the algorithm where it’s most needed. It’s a small time investment that makes a real difference in downstream data quality.
To learn more, visit the full tutorial on protein docking with Hex inside SAMSON.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net