Protein docking is a powerful tool in structural biology, but one frustrating aspect many molecular modelers share is this: you set up your system, launch a docking calculation, and… the results are off. 🧬
They aren’t necessarily bad, but the top poses don’t make sense. Why? In many cases, it’s not the method — it’s the parameters.
This post takes a closer look at some essential Hex parameters within the SAMSON platform that often confuse or trip up new users. Tuning them just right can save hours of computation and give you better biological insight.
Finding the Signal in the Noise: Correlation Type
One of the first decisions you’ll make in Hex is choosing the correlation type: Shape-only or Shape + electrostatics. If your proteins carry complementary charges, using electrostatics can significantly improve results. But beware — if you’re docking DNA or RNA, applying electrostatics may mislead the algorithm, so in those cases, stick to Shape-only.
Sampling Method: Exploring the Search Space
Another impactful parameter is the Sampling method. Switching from Full rotation to Range angles allows for focused searches near known or suspected binding sites. This is particularly helpful if your biological target is known, and can cut down drastically on false positives.
Speed vs. Accuracy: Steric Scan and Final Search
Hex uses a two-step docking approach: a fast approximate Steric scan followed by a more precise Final search. Setting the Steric scan order between 16–18 and the Final search order up to 25–30 is typically a good balance.
💡 Tip: The higher the Final search order, the finer the resolution. But calculations will take longer. For high-resolution crystal structures with minimal conformational flexibility, go with N=30; for predicted or flexible structures, N=25 is usually enough.
Advanced Parameters: Visual Tools Can Help
The real power comes when you activate Advanced parameters and use Range angles. SAMSON visualizes the search cones:
Set the rotational range angles for both receptor and ligand to 45 degrees if you already know the binding site. This limits the search area and makes the process more efficient — both in terms of time and docking relevance.
Post-Processing: Don’t Skip It
After finding possible poses, Hex offers Bumps Counts and Molecular Mechanics (MM) Refinement. These post-processing options help filter out biologically unrealistic poses. Even if it’s still marked as an alpha feature, MM Refinement significantly prunes noisy solutions and helps prioritize better-scoring complexes.
Conclusion
Docking predictions are only as good as the thought put into parameter selection. If you know (or strongly suspect) the binding region, use advanced sampling settings. Be cautious with electrostatics, and don’t forget to refine before interpreting biological meaning.
For a step-by-step tutorial, check the original SAMSON documentation for Hex Extension: https://documentation.samson-connect.net/tutorials/hex/protein-docking-with-hex/
SAMSON and all SAMSON Extensions are free for non-commercial use. Get the platform at https://www.samson-connect.net.