Protein-protein docking is one of the cornerstones of structural bioinformatics, but it can be computationally expensive – especially when conformational sampling is performed across broad orientations. One way to make docking significantly faster and more relevant is to limit the sampling domain intelligently. In this post, we explore how SAMSON’s Hex Extension allows molecular modelers to define search domain constraints using range angles — an efficient way to accelerate docking while improving prediction quality.
Why Limit the Search Domain?
By default, docking tools scan a vast range of orientations when searching for receptor-ligand binding conformations. If no prior information is used, the search domain covers the entirety of possible orientations (typically, a full 180° rotation range around key axes), which can:
- Significantly increase computation time
- Produce many irrelevant docking modes in unwanted locations
However, if you’re aware of approximate binding sites (via homology, experimental data, or educated guesses), limiting the sampling range using range angles is a highly practical solution.
Setting Up Range Angles in Hex
In SAMSON, when using the Hex Extension, you can define the angular search domain through range angle constraints. To do that:
- Ensure the Sampling method is set to Range angles.
- Click on Advanced parameters.
- Set Receptor angle range and Ligand angle range. A value of 45° is usually a good starting point when you want to constrain near an expected binding orientation.
This setup creates conical search regions around the axes connecting protein centers. It’s especially useful when the interface residues or general binding zones are already known or guessed. Orient the ligand near the expected interface first, then define the angular cones.
In this example, the cones indicate the limits of angular exploration during docking. It ensures that only orientations within that region are evaluated in the docking search, reducing both false positives and calculation time.
Useful Tip: Twist Angle
The Hex Extension also lets you set the Twist angle range, i.e., the rotation of the ligand around the intermolecular axis. Adding this constraint further refines the rotation space, especially when certain torsional orientations are physically unlikely or experimentally excluded.
How Much Time Can You Save?
Limiting the range angles doesn’t just speed up computation — it increases the specificity of your docking solutions. When precision is critical or you’re iterating through many ligands or receptor variants, the time and relevance benefits greatly add up.
To recap, here’s when to use angular constraints:
- You have an idea of the binding region.
- You want to reduce docking time.
- You need to increase docking specificity for comparative modelling.
Putting It Into Practice
Once you’ve adjusted the range angles, proceed with the docking as usual. The solutions will appear as clusters in the Results tab, each corresponding to a docking pose within the defined sampling domain. You can animate through them, export conformations, or refine them further using Hex’s integrated post-processing tools.
Defining a targeted search domain is a simple step, yet it often leads to much more insightful and efficient docking workflows.
To learn more, visit the full documentation page on SAMSON’s website: Protein docking with Hex.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at www.samson-connect.net.