When modeling protein conformational changes, efficiency matters. Exploring the full atomistic flexibility of a large biomolecule can be time-consuming and computationally expensive. This is where smart simplification strategies like the As-Rigid-As-Possible (ARAP) method come in handy — especially when using SAMSON’s Protein Path Finder app.
ARAP allows you to designate a subset of protein atoms as active, meaning these atoms drive the motion, while the rest react accordingly in a physically meaningful way. This technique can dramatically simplify your search for transition paths between two protein conformations, such as from open to closed states.
Why Selecting Active Atoms Matters
Choosing the right active atoms allows you to:
- Reduce the search space, making computations faster.
- Bias the path search towards biologically relevant motions.
- Improve the interpretability of resulting conformational transitions.
But what should you choose as active atoms? In practice, these are usually atoms associated with flexible or functionally significant regions of the protein, such as mobile domains.
Step-by-Step: Defining Active Atoms with ARAP in SAMSON
In the Protein Path Finder tutorial, a pair of alpha-carbon (CA) atoms from two distant residues is used as an example: GLY 12 and ARG 123 of Adenylate Kinase. These residues belong to different domains which move during the protein’s conformational change – a logical choice.
Use the structured document provided in the tutorial or your own system. Here’s how to assign the active atoms:
- Find the predefined group in the Document view:
It’s calledCA in GLY 12 and CA in ARG 123. - Double-click the group to select the atoms.
- Click the Add button in the Protein Path Finder app to set them as active ARAP atoms.
This minimal yet carefully selected set of atoms will control the protein’s motion, while the rest of the molecule will follow based on ARAP modeling.
In the Advanced information panel of the app, you’ll see how many active atoms have been added. A visual representation will appear with active atoms in green.
Advanced Tip: Use Node Specification Language
If you’re working with your own model and need to select atoms programmatically, use SAMSON’s Node Specification Language (NSL). For example:
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("CA" in "GLY 12") or ("CA" in "ARG 123") |
This selects exactly those atoms based on their names and residue identifiers — useful for automating repetitive selections or working in scripts.
Want to try with your own system? You can also define groups for active atoms based on domain boundaries or hinge regions — the critical parts that usually drive functional motion.
What Happens Next?
Once you’ve defined the active atoms, you can proceed to specify the sampling region for them and jump into the protein path search using the ART-RRT method. From there, you’ll be able to retrieve low-energy transition paths efficiently.
Learn more, including how to perform constrained minimization, track energy profiles, and export the results at the full Protein Path Finder tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON on SAMSON Connect.