One common challenge in molecular docking is achieving the right balance between search accuracy and computational efficiency. When modeling protein-protein interactions, researchers often want results that are both physically meaningful and delivered in a reasonable amount of time. But how can you reduce false positives and cut down on computation time—without missing critical orientations?
This is where narrowing the search domain in Hex, via range angles, makes a big difference. In this post, we’ll look at how to configure a more targeted protein docking setup using the Range angles feature in Hex for SAMSON.
Why Restrict the Search Area?
By default, Hex explores docking orientations across the entire spherical globe around the receptor. While comprehensive, such exhaustive sampling takes more time and tends to produce numerous false-positive docking modes. If you already have structural insights—such as approximate interface locations—narrowing the sampling via angular constraints can result in stronger predictions, in less time.
How to Set Range Angles in Hex
In the Hex interface inside SAMSON, begin by setting the Sampling method to Range angles. Then click on Advanced parameters to manually define your angular constraints.
Hex allows you to specify three angles to guide the docking search:
- Receptor angle range: Maximum rotation for the receptor.
- Ligand angle range: Maximum rotation for the ligand.
- Twist angle range: Rotation around the axis connecting centers of the two proteins.
These angles define spherical cones centered on each molecule, and their apex points to the corresponding center of geometry. By default, they are set to 180°, meaning no restrictions. To guide Hex to focus around a known or assumed binding orientation, reduce these values. A 45° range is a good starting point for loosely limiting the search.
Getting the Proteins in Place
Before applying angular constraints, it’s helpful to manually position the ligand near the expected binding site. You can use SAMSON’s Move editors to rotate and align the ligand appropriately. This manual adjustment ensures the defined cones actually capture the relevant interaction zone.
Why This Technique Helps
By reducing the search domain, you:
- Speed up the docking process
- Reduce the number of improbable solutions
- Concentrate sampling effort on biologically plausible conformations
It’s an effective way to use your domain knowledge to guide an otherwise fully automated process.
Want to Learn More?
Learn more about matching docking parameters to your molecular system in this tutorial from the SAMSON Documentation Center: Protein docking with Hex.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.