One of the most common challenges molecular modelers face during protein-protein docking is handling the vast number of potential orientations and false positives generated during the search. Even when docking crystal structures, an unrestricted search can lead to misleading predictions or excessive computation times.
Thankfully, in SAMSON’s Hex Extension, it’s possible to significantly narrow down the docking search by adjusting the range angles during the setup of the search domain. This technique is especially useful when you already know or suspect the location of the binding site between two proteins.
What Are Range Angles?
Range angles in Hex define a spherical cone centered on the intermolecular axis that connects the centers of the receptor and ligand. Only docking orientations that fall within this cone are considered. The twist angle can also be constrained around this axis. By default, the Range Angle is set to 180 degrees (i.e., the entire sphere is sampled), which means no prior knowledge is used to guide the docking.
Instead, setting the Range Angle to a smaller value, such as 45 degrees, can steer the docking search toward more relevant orientations, potentially avoiding sterically incompatible or energetically unlikely conformations. This guidance not only improves docking reliability but also reduces computation time and memory usage.
How to Set Up Range Angles in SAMSON
Once you’ve launched the Hex App in SAMSON (Home > Apps > Biology > Hex), you’ll need to:
- Set the Sampling method to Range angles.
- Click on Advanced parameters to reveal angle settings.
- Manually move your ligand close to the expected binding site of the receptor. You can use the Move editors to assist in precise placement.
- Reduce the Receptor and Ligand range angles to a more focused value (e.g., 45 degrees).
Once both cone angles are set, Hex will visualize them as transparent cones connecting the two proteins. These cones define the ‘allowed’ orientations, helping eliminate orientations that are spatially irrelevant.
Why It Matters
Limiting the angular search domain is especially valuable when docking flexible or ambiguous structures, or when time and computational cost are concerns. It helps to:
- Improve prediction accuracy by focusing around experimentally-supported regions.
- Reduce the number of non-physical results (false positives).
- Accelerate docking runs by shrinking the search space.
This approach becomes very powerful when combined with prior biological knowledge, such as known interaction interfaces, mutagenesis data, or electrostatic complementarity between binding regions.
You can also combine this with tweaks to the correlation type, post-processing filters, and visualization models to further analyze which conformations are likely to be biologically relevant.
To learn more about limiting the search domain and all parameter setups in Hex, check out the full 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 get SAMSON at https://www.samson-connect.net