One commonly overlooked yet crucial step in modeling protein conformational transitions is setting up the sampling box. If you’ve struggled with generating relevant pathways or wondering why you’re getting unexpected motions, it’s likely that your sampling region is not well defined. Fortunately, SAMSON’s Protein Path Finder app offers a clear and flexible way to control this aspect of your simulations.
Defining a good sampling box allows you to guide the search for conformational transitions. In Protein Path Finder, the sampling box operates on active ARAP atoms — typically a small set of strategically chosen atoms (e.g., alpha-carbons) whose movement effectively drives the rest of the structure through an ARAP interpolation.
What Is the Sampling Box?
The sampling box defines the region in space within which the active atoms are allowed to move during the motion planning algorithm. This region acts as a soft boundary, biasing the transitions generated by the ART-RRT method. Controlling its size and location helps prevent unrealistic conformations or overly broad searches that waste computing time.
By default, the sampling box encompasses all protein atoms in both the start and goal conformations. While this is a safe starting point, it’s often too broad for efficient searches and accurate modeling. Customizing the box to better fit your system can significantly improve your results.
Setting the Sampling Box in SAMSON
Once your system is prepared and your active atoms selected, unfold the Set the sampling box for active ARAP atoms section in the Protein Path Finder app. You’ll see a cubic green box appear in the viewport, centered around your active atoms.
You can set each dimension of the box independently or specify a uniform cube. A typical practice is to constrain it just enough to allow realistic movement but restrict unphysical distortions. For instance, a cube of 200 Å per side was used in the tutorial example, providing enough room for moderate domain motions.
Best Practices & Tips
- Choose active atoms wisely: The effect of the sampling box is only as good as the atoms it influences. Typically, two well-separated alpha-carbons are a reliable choice.
- Start with a larger box and gradually reduce it once you’re familiar with the system’s behavior. An overly tight box may prevent any useful conformations from being generated.
- Use visualization: The green preview box updates in real time. Visually assess whether it covers the movement range you expect between conformations.
- Understand the bias: A skewed or asymmetrical box will favor certain directions of movement over others, which can be used strategically in cases where you have experimental insight.
By carefully setting the sampling box, you’re not just limiting motion — you’re guiding it through a meaningful part of the conformational landscape. Small adjustments can lead to more efficient calculations and more physically relevant transition paths.
Want to go further? Explore the full Protein Path Finder tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at https://www.samson-connect.net.