A protein–protein docking run can spend time exploring orientations that are unlikely to matter. If you already have clues about where two proteins interact, an unrestricted search may be unnecessarily broad. The challenge is to use those clues to reduce the search without constraining the proteins so tightly that plausible poses are excluded.
In SAMSON, the Hex Extension offers a way to do this with Range angles. This approach is most useful when you have a reasonable starting orientation or know which regions of the receptor and ligand are likely to form the interface. If you have no idea where the interface is, restricting the search based on a guess can bias the result; begin with a broader search instead.
What a range angle does
Hex describes the docking search using spherical coordinates. The receptor and ligand have origins, and an intermolecular axis connects them. A range angle defines a cone around that axis: only angular samples within the cone are considered. A range of 180 degrees corresponds to no angular constraint, while a smaller value narrows the orientations included in the search. In the range-angle search, the ligand is rotated and positioned around the receptor.
This is a search-space control, not proof that a pose is correct. A narrower search can reduce unnecessary exploration, but it also depends more heavily on whether the starting placement and the assumed interface are sensible.
A practical setup
- Prepare the structures. Remove alternate-location atoms, water, monatomic ions, and ligands if present. Add hydrogens if needed, while preserving hydrogens that already reflect a chosen protonation state. If residues or heavy atoms are missing, the PDBFixer Extension can be used to repair the structure.
- Assign the partners. Open Hex from Home > Apps > Biology > Hex, then select the receptor and ligand in the document and set each in the Hex interface. Save the ligand’s initial conformation if you may want to repeat the calculation with different settings.
- Choose the search method. Set Sampling method to Range angles, then open Advanced parameters.
- Orient before narrowing. If the binding-site location is known, move and rotate the ligand so it is near the expected site. SAMSON’s Move editors can be used to translate and rotate it.
- Set conservative limits first. The tutorial demonstrates setting both receptor and ligand range angles to 45 degrees. Treat this as an example, not a universal setting: choose limits in light of how certain you are about the starting orientation. You can also limit the ligand’s twist rotation about the intermolecular axis.
Balance speed with coverage
Hex can also use a low-resolution Steric scan before the higher-resolution Final search. The first phase covers the space more coarsely, helping reduce the number of orientations passed on for finer evaluation. The tutorial notes that a Steric scan order of 16–18 is sufficient in many cases, and gives example combinations of N=16 with a Final search of N=25, or N=20 followed by N=30. A Final search order of N=25 is generally used for more flexible or model-built structures; N=30 is recommended for high-resolution crystal structures when binding-related conformational changes are expected to be small.
For a first pass, resist the temptation to make every setting as restrictive as possible. If the interface is uncertain, broader angular coverage may be more appropriate. If the site is known, a carefully oriented ligand and narrower ranges can make the calculation more focused. Keep track of the starting conformation and settings so you can compare runs rather than relying on memory.
Read poses as candidates, not answers
After docking, inspect the Results tab: modes are clustered, and you can view the best-scoring mode per cluster or all modes. Selecting a row restores that ligand conformation; right-clicking a row lets you create a conformation in the document. Compare plausible poses visually and examine contacts or hydrogen bonds with analysis tools. A score or a restricted search alone does not establish that a predicted complex is biologically correct.
For the complete workflow and parameter details, see the Protein docking with Hex tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.