One recurring pain in protein-protein docking tasks is the enormous search space. When both proteins are allowed to freely align in all orientations, the number of possible docking poses quickly becomes unmanageable. This not only increases computation time but also adds to the noise of false-positive results that researchers have to sift through.
In SAMSON, when using the Hex Extension for protein docking, it’s possible to significantly restrict the search domain by adjusting the range angles for the receptor and the ligand. This often-overlooked feature can help focus computational resources on the most biologically relevant regions and reduce docking time considerably.
What is a Range Angle?
The range angle describes a spherical cone centered on the line connecting the centers of the two proteins. It defines the segment of this space in which the ligand or receptor is allowed to rotate during docking.
By default, Hex uses a full 180-degree range angle—meaning the entire surface of the receptor is considered for potential docking sites. But if you already know or suspect where binding may occur, refining this angle (for example to 45 degrees) helps constrain the docking process around that region.
How to Set It Up in SAMSON
To configure the search domain using range angles in the SAMSON platform, follow these steps:
- Open your project and select the Hex app via Home > Apps > Biology > Hex.
- In Hex, set the Sampling method to Range angles.
- Click on Advanced parameters.
- Adjust the Range angle for the receptor and the Range angle for the ligand to desired values—e.g., 45° for each.
You’ll immediately see the impact: a pair of cones (as shown below) illustrating the constrained docking zones for both proteins.
The apexes of these cones are placed in the centers of the receptor and ligand molecules, and only configurations within these cones are explored during the docking process. This significantly narrows down the number of poses being evaluated.
When Should You Use Range Angles?
Range angle filtering is especially useful when:
- You have prior knowledge about binding interfaces, e.g., from literature or mutagenesis data.
- You want to test binding hypotheses in a specific region.
- You are docking structures that are relatively rigid (i.e., high-resolution crystal structures).
For instance, if you’re docking an enzyme with an inhibitor known to bind near the active site, aligning the ligand close to this region and limiting the angle helps shorten computation time and improves the relevance of docking results.
Bonus: Also Limit the Twist
Along with range angles, you can adjust the twist angle of the ligand. This refers to bond rotation around the intermolecular axis—useful for further narrowing down feasible orientations.
Final Notes
Using these angle constraints lets you bring biological intuition into protein docking, avoiding exhaustive blind searches. It’s simple to set up in SAMSON and can make a real difference in time and relevance of your results.
To learn more about docking with the Hex Extension in SAMSON, including how to prepare, set up, run, and analyze docking simulations, visit the official documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON by visiting https://www.samson-connect.net.