Avoid Transition Path Errors: Aligning Start and Goal Conformations in SAMSON

One common stumbling block when modeling conformational transitions in proteins is making sure your start and goal structures are properly defined—and actually compatible with each other. If the structural data going into your simulations isn’t prepared consistently, your modeling pathways may show unrealistic motions or fail to converge altogether. Fortunately, SAMSON provides a straightforward method for setting up your system correctly using the Protein Path Finder app.

This blog post highlights an important preparatory step: how to set the start and goal conformations for a protein transition study. We’ll also touch on some useful practices to avoid structural mismatches that can derail your modeling workflow.

Choosing and Extracting Protein Conformations

Once you’ve opened your sample or custom protein structure in SAMSON, the Protein Path Finder tool allows you to extract conformations directly from the active document. For example, in the built-in Adenylate Kinase tutorial, the document contains two conformations representing the PDB entries 4AKE and 1AKE—available as start and goal. These can be retrieved easily by clicking the Get conformations from the active document button.

Select the appropriate structures in the “Start conformation” and “Goal conformation” dropdowns. These choices define the endpoints of your conformational transition path.

Important: If you use your own model, make sure your two conformations are aligned in structure and residue identity. Both conformations should:

Contain the same atoms in the same order
Use consistent chain identifiers
Have no differences in residue numbering

Combining Your Own Conformations

If your conformations are stored in two separate files (as is often the case when downloading different PDB structures), you’ll need to combine them into a single PDB file with two models:

MODEL        1
... (start conformation)
ENDMDL
MODEL        2
... (goal conformation)
ENDMDL
END

MODEL 1

... (start conformation)

ENDMDL

MODEL 2

... (goal conformation)

ENDMDL

END

After importing this new file into SAMSON, you can follow the same steps to detect conformations from the document and select them as start and goal positions.

If your structures differ slightly (e.g., missing atoms, ligands, alt positions), prep work is essential. The PDBFixer extension helps fix such issues and allows you to add hydrogens for a specific pH. Alternatively, follow the more complete guide on Protein Preparation & Validation.

Bonus Tip: Use Node Specification Language (NSL)

To check or reference specific atoms or residues—like identifying active atoms for the motion—you can use SAMSON’s NSL. For example, to select alpha carbons in specific residues:

("CA" in "GLY 12") or ("CA" in "ARG 123")

1	("CA" in "GLY 12") or ("CA" in "ARG 123")

Conclusion

Taking a few extra moments to verify and properly define the start and goal conformations can save you hours later. Whether you’re using built-in SAMSON samples or your own PDB structures, alignment and consistency are key prerequisites for accurate path exploration.

Learn more about setting up protein transitions and modeling them with ART-RRT in the full Protein Path Finder tutorial.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.