When modeling protein transitions — for instance, switching between open and closed conformations — a surprisingly common obstacle is just getting the input right. If your two conformations come in separate PDB files, you might scramble to align and manage them with additional tools. This quick guide shows how you can prepare your inputs cleanly in SAMSON for the Protein Path Finder app and skip several common pitfalls.
Let’s say you have two conformers of a protein, one as 4AKE and the other as 1AKE. To find a smooth pathway between them using the Protein Path Finder, they need to be in a single PDB file with consistent structures.
Why preparation matters
The path-searching algorithm used in the Protein Path Finder relies on a consistent mapping between atoms in the two states. If one structure has missing residues or extra water atoms while the other doesn’t, the comparison breaks — and the algorithm can’t connect them.
Here’s how to avoid that situation step-by-step.
Step 1: Clean up individual files
In SAMSON, go to Home > Prepare and use these options:
- Remove alternate locations
- Remove ligands, solvent, and ions
- Add hydrogens
This helps create consistent systems by stripping the structures down to the protein backbone and standardizing hydrogenation.
Step 2: Fix inconsistencies with PDBFixer
If either file has missing heavy atoms or residues, use the PDBFixer extension. It can restore side-chains, fill gaps, and add hydrogens for a chosen pH.
Step 3: Merge conformations into one file
The planner requires that both conformations be present as two models inside a single file. You can create this manually by concatenating your PDB files into a single PDB using this format:
|
1 2 3 4 5 6 7 |
MODEL 1 ... <-- contents of first conformation ENDMDL MODEL 2 ... <-- contents of second conformation ENDMDL END |
Save this merged file and load it into SAMSON. Now, each conformation is treated as a separate model within the same system, making it compatible with the Protein Path Finder.
Shortcut: use the tutorial sample system
The official Protein Path Finder tutorial provides a pre-prepared example with the two conformations already cleaned and stored in a single document. You can load it directly from this link:
https://www.samson-connect.net/documents/5eb7990e-fa44-4595-ab2c-99b6c68eada9
Key takeaway
Proper system preparation isn’t just a technicality — it’s central to ensuring smooth and meaningful transition path generation for proteins. With the steps above, you’ll eliminate setup errors that often lead to wasted time or invalid results.
To learn more, refer to the full documentation here: Protein Path Finder – SAMSON Documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.