Before diving into modeling the dynamic transitions of proteins, there’s one crucial step that often gets overlooked – correctly preparing your molecular systems.
This seemingly simple process can make or break the results you get from advanced tools like the Protein Path Finder in SAMSON. Many molecular modelers wonder why their simulations don’t result in successful or meaningful paths between conformations. In many cases, the culprit lies in the system setup — particularly when handling multiple conformations from different files, missing atoms, or inconsistent protein chains.
This article walks through a key challenge: How to prepare your protein system when your conformations are in separate files, using built-in SAMSON extensions, with a focus on good practices and tips that help scientists avoid hidden pitfalls.
Why proper system preparation matters
When performing conformational path analysis, such as with the ART-RRT method used in SAMSON’s Protein Path Finder, both start and goal conformations must be structurally identical — not just visually similar. Differences in residue naming, atom order, or missing residues can cause path-finding to fail or produce misleading results.
Step-by-step: Preparing and merging two conformations
If your starting and ending conformations are stored in different structure files (e.g., two PDB files), here’s what you need to do in SAMSON:
1. Clean and fix each model independently
- Go to Home > Prepare.
- Remove alternate locations, ligands, solvent, and ions.
- Add hydrogens to each structure.
- If residues or heavy atoms are missing, use the PDBFixer extension to complete your model.
This ensures each conformation is chemically correct and complete.
2. Merge them as different models
For the path-finding algorithm to work, the structures need to be in a single file with consistent atom naming and ordering. You can manually edit and concatenate the files using this format:
|
1 2 3 4 5 6 7 |
MODEL 1 ... (first conformation) ENDMDL MODEL 2 ... (second conformation) ENDMDL END |
This format ensures the Protein Path Finder recognizes two distinct models within the same structure document.
3. Load into SAMSON
Once the two conformations are combined into one PDB file and loaded into SAMSON, you can proceed to define the conformations in the Protein Path Finder by using the Get conformations from the active document button.
Good practice: Check structure consistency
Always verify that chains, residues, and atoms are present and ordered consistently across both conformations. A slight change in atom indexing can cause the algorithm to misinterpret the difference as a structural change or mismatch.
If in doubt, open both models in SAMSON and compare them before merging.
Prepare once, simulate smoothly
Correctly preparing your protein model ensures that the path-finding stage proceeds without errors or confusion. It also ensures that your results are accurate and reproducible. Even if your modeling platform is powerful, the output quality still relies on a clean and structurally consistent input.
For more details on using the Protein Path Finder in SAMSON or to learn about defining sampling regions and search parameters, please visit the full documentation page here: Protein Path Finder Documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.