When performing protein-protein docking, modelers often face a critical tradeoff: how to balance docking accuracy with efficient computation. Complex systems can take hours to dock, especially if you’re exploring the full 3D orientation space of the ligand relative to the receptor. What if you could reduce this time significantly, without sacrificing much predictive power?
The Hex Extension in SAMSON offers a practical way to boost docking efficiency using range angles. This method narrows the search domain based on known or suspected binding sites, saving precious compute time — and it’s easier to use than you might think.
Why Range Angles Matter
Hex’s docking algorithm works in spherical coordinates, rotating the ligand around the receptor to explore possible binding conformations. By default, both receptor and ligand are free to rotate across the full 180° hemisphere, resulting in a full spherical search. While exhaustive, this is computationally heavy, especially for large proteins.
But if you already suspect or know the interface residues — or just want a faster result for screening — you can reduce these angles using range angle constraints. The idea is to orient the receptor and ligand in an initial pose close to the expected binding conformation, and then limit how much each can rotate.
Setting Up Range Angles
Once you’ve opened the Hex Extension via Home > Apps > Biology > Hex, and defined your receptor and ligand, follow these steps:
- Set the Sampling method to Range angles.
- Click on Advanced parameters.
- Adjust the Receptor angle range and the Ligand angle range sliders. A value of
45°is a common choice to limit the angular space without being too restrictive.
These angle constraints visually appear as cones, with their apexes at the centers of the two proteins. Only docking conformations falling within these cones will be evaluated, focusing the computational power where it matters most.
Fine-Tuning Further
You can also set the Twist angle range – this controls rotation of the ligand around the intermolecular axis (i.e., the axis connecting the two protein centers). Similar to the range angles, this further restricts orientations to be evaluated, potentially reducing docking noise from undesirable conformations.
💡 Pro tip: Use SAMSON’s built-in Move editors to position the ligand manually near the suspect binding site before setting the constraints. The closer you are to the native pose, the more effective the angular restriction will be.
Typical Use Case
Let’s say you load the example system with proteins 2PTC_E and 2PTC_I. If you already have a rough idea of their binding interface, rotate 2PTC_I so it faces 2PTC_E, and then apply 45° angle constraints to both.
This step transforms a potentially time-intensive docking procedure into one that completes in minutes — especially useful when running multiple dockings with varying parameters.
When Should You Use It?
- 📍 You know or can predict the interface residues.
- 🧪 You’re screening multiple ligands and time is limited.
- 🧬 You want to reduce false positives during predictive modeling.
To explore all these settings and see example visuals, visit the full tutorial here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.