If you’ve ever performed protein-protein docking using tools like Hex, you’ve probably encountered this common challenge: docking takes time, especially when the search space is large and the receptor and ligand can explore orientations across the full 360° sphere. While this is necessary in some exploratory scenarios, in many cases you have more information—like a known binding region—and you’d rather speed up the process.
Hex, integrated in SAMSON, makes it possible to constrain the docking calculations to more relevant areas by restricting orientations through range angles. This can drastically reduce false positives and computing time, especially when structures are already pre-positioned close to each other. Here’s how it works.
When and Why to Limit the Search Domain
Constrained searches are particularly useful when one or both protein interfaces are known. If you’re modeling a known complex or interested in a specific binding mode, letting the ligand explore every possible angle may be unnecessary—and computationally expensive. Instead, Hex allows you to control how much the ligand and receptor can rotate through “range angles” and “twist angles.”
Step-by-Step Setup in SAMSON
To limit the docking search in Hex:
- In SAMSON, open the Hex application via Home > Apps > Biology > Hex.
- Set your proteins as receptor and ligand respectively (for example,
2PTC_Eas receptor,2PTC_Ias ligand). - Choose the sampling method: select Range angles from the available dropdown options.
- Click on Advanced parameters to bring up the controls for search space restrictions.
From there, you can set the rotation ranges for both the receptor and ligand. A value of 180 means full spherical exploration. A lower value, like 45 degrees, creates a cone-shaped sector that reduces orientation combinations and speeds up search times.
Pro tip: Position your ligand near the expected binding site using SAMSON’s move tools first, and then reduce angular ranges. This ensures the binding orientations stay around this initial configuration, improving efficiency and relevance.
Twist angle range offers an additional control over the ligand’s rotation around the axis that connects the centers of the receptor and ligand. You can restrict this too, if the docking doesn’t require full 360° flexibility.
Once you’ve specified these values, you’ll see visual cones around the molecules that show the limited angular sampling zones:
These cone visuals make it easy to verify the constraint settings and adjust them as necessary before running the docking search.
Benefits at a Glance
- ⏱️ Faster computations: Reducing the search space speeds up docking significantly, especially helpful if you’re testing multiple conditions.
- 🎯 More relevant solutions: Focused searches help avoid potentially misleading docking results from irrelevant orientations.
- 📐 Greater control: Customizing receptor and ligand orientation allows you to fine-tune searches based on prior biological knowledge.
While unconstrained docking is great for exploration, limiting your search domain using Hex’s range and twist angles is often a smarter, more efficient approach to get biologically meaningful results more quickly.
To learn more about how to use these features and set up your docking runs in Hex and SAMSON, check the full documentation page here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.