One common challenge in molecular modeling is reducing protein docking times without compromising the quality of results. When you already have an idea of the binding site location, unconstrained searches can become unnecessary and slow. This blog post introduces a little-known but impactful strategy: using range angles to constrain the docking search space in the Hex extension for SAMSON.
Hex uses spherical coordinates to perform docking, meaning the ligand is rotated and translated around the receptor within a spherical region. By default, both proteins are considered to be rotatable through a full 180°, which maximizes search coverage but also drastically increases computational time. However, if you already have structural or experimental clues about where binding should occur, you can limit this spherical search using range angles.
What Are Range Angles?
Range angles define a spherical cone centered on the axis connecting the centers of the two proteins. Instead of sampling the full spherical range, Hex restricts orientations to lie within this cone. Limiting the receptor and ligand range angles to smaller values—say, 45°—keeps conformations focused on the likely binding interface.
Step-by-Step: How to Constrain the Search
1. Open the Hex application inside SAMSON (Home > Apps > Biology > Hex).
2. Set the Sampling method to Range angles.
3. Click on Advanced parameters to access the angular constraints.
4. Adjust the Receptor angle range and Ligand angle range to suitable values. A typical value when you have a rough idea of the binding location is 45°.
5. Optionally, set a Twist angle range to further constrain the ligand’s rotation around the intermolecular axis.
6. The docking visualization in SAMSON will then show two cones (one per protein) around the intermolecular axis, clearly indicating the constrained regions.
Why This Matters
Constrained searches are useful in multiple situations:
- You know the approximate binding site from previous studies.
- You want to run multiple parameter combinations quickly.
- Your receptor or ligand is especially large, making full rotational searches computationally expensive.
This technique doesn’t just save time—it also reduces the number of false positives in your docking results, by focusing the search on the biologically relevant zone.
A Note on Orienting the Ligand
Before applying these constraints, it’s good practice to manually orient the ligand towards the correct binding area. This can be done using SAMSON’s Move editors. Once the ligand is roughly aligned, setting narrow range angles becomes much more effective.
Conclusion
Constraining the docking search domain using range angles is a practical way to speed up calculations and improve focus around known or suspected binding sites. If you’re spending too much time waiting for docking runs to finish, or seeing irrelevant conformations, this is a small change that can deliver significant gains.
To learn more about setup and usage of the Hex app within SAMSON, visit the official documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.