Protein docking can be a time-consuming process, especially when dealing with flexible structures or large systems. Many molecular modelers face a common challenge: how to reduce docking search time without compromising accuracy. One actionable strategy is to narrow the docking search domain using range angles in the Hex Extension for SAMSON.
This approach helps the Hex docking engine focus on a smaller region of conformational space when you already have some idea of the binding interface or location. It’s particularly useful for high-resolution structures where only subtle conformational changes are expected on binding.
When and Why Use Range Angles?
By default, protein docking in Hex is performed over 180° rotational angles between the receptor and ligand. This brute-force approach may not be necessary if you know roughly where the interaction is likely to happen. Using range angles lets you narrow down the search domain to target that specific zone. That means faster runs and fewer false positives.
This method is ideal for scenarios when:
- You know the region of the receptor involved in binding
- You’ve pre-positioned the ligand close to a known pocket
- You want to iteratively refine docking results
How to Set Range Angles
In the Hex app in SAMSON:
- First, set the Sampling method to Range angles.
- Click on Advanced parameters.
- Adjust the Receptor angle range and Ligand angle range. A value of 45° is often a good starting point to target a localized search domain.
Visually, you’ll see two cones representing the rotational freedom of the receptor and ligand around an intermolecular axis. These cones define where the docking engine will do its search:
Only orientations within these cones will be considered. This reduction in orientation space directly reduces the computation time needed for docking.
Optional: Limiting Twist Rotation
You can further fine-tune the search by setting a Twist angle range, which controls the torsion about the axis connecting the molecule centers. This step is beneficial when ligand orientation around the binding axis matters.
Aligning Before Docking
If the ligand is not initially near the expected binding site, use the move tools to manually position it. This pre-orientation step increases the value of narrowing the angular range. Aligning ensures that the restriction makes sense spatially and doesn’t cause the search to miss the actual binding conformation due to misplacement.
To move the ligand, you can use one of the Move editors available in SAMSON.
When to Avoid Narrowing
Not all docking cases are suited for this optimization. Broad searches (180°) might still be needed when:
- Binding interfaces are unknown
- Large conformational changes are expected
- No prior orientation between receptor and ligand exists
Quick Tip
Start with a 45° cone for both receptor and ligand. If docking fails to converge or misses poses, slightly widen the angles. It offers flexibility via fast iteration.
To learn more, see the full SAMSON Hex docking tutorial:
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 at https://www.samson-connect.net.