When modeling conformational transitions in proteins, ensuring that the start and goal structures are properly aligned and compatible is essential. If your starting and ending conformations are not set up correctly, most path-finding algorithms will either fail or return meaningless results. In this blog post, we’ll walk through how to prepare start and goal conformations using the Protein Path Finder app in SAMSON — a common but easily overlooked source of error for many molecular modelers.
Why proper setup matters
Molecular modeling tools often require your system to be chemically and structurally consistent. This is especially important when you’re computing transition paths between two conformations of the same protein. If your PDB files differ — even slightly — in chains, residues, or atoms, the process won’t be valid.
How to prepare your system
If your conformations are contained in two separate PDB files, you’ll need to merge them manually into a single file. This involves ordering them as separate models like this:
|
1 2 3 4 5 6 7 |
MODEL 1 ... (start conformation) ENDMDL MODEL 2 ... (goal conformation) ENDMDL END |
Make sure both conformations have:
- The same number and order of chains
- The same residue sequence
- Identical atom names and ordering
Inconsistencies between the start and goal models — such as missing atoms or residues in one model but not the other — will complicate downstream computations.
Fixing common issues
If your model is incomplete — e.g., missing hydrogens or residues — the PDBFixer extension in SAMSON can help you:
- Add hydrogens
- Repair side chains with missing atoms
- Fix missing residues
Additionally, you might want to use SAMSON’s Home > Prepare tool to:
- Remove alternate locations
- Remove ligands, solvent, and ions
Once you’re confident in your models, concatenate them into one file as separate MODEL blocks, and load them into SAMSON.
Choosing Start and Goal
After loading your concatenated model into SAMSON, open the Protein Path Finder app and click on Get conformations from the active document. This will populate the app with available models.
From there, select which one will be your start conformation and which will be your goal conformation using the dropdown menus under Start conformation and Goal conformation.
You’re now ready to configure your transition path planning.
Visual Confirmation
Once you select your conformations, it’s a good idea to verify them visually in the document view. SAMSON will show the two extreme conformations and allow you to preview how the transition will start and end.
Conclusion
Setting up start and goal conformations might seem trivial, but small mistakes in preprocessing can lead to significant downstream issues. Taking the time to validate structural consistency and preparing the input PDB file correctly can save hours of troubleshooting later.
To learn more, you can read the full tutorial here: Protein Path Finder documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use.
Download SAMSON at https://www.samson-connect.net.