Gearing Up for Protein Transition Pathways: Setting Up Start and Goal Conformations in SAMSON

When studying large-scale protein motions or conformational changes, especially in enzymes or signaling proteins, it often becomes critical to trace plausible transition pathways between two experimentally observed or predicted conformations. But before you begin applying multiscale planning algorithms like ART-RRT, there’s one major step that can be confusing and time-consuming for many molecular modelers: choosing and setting up the start and goal conformations.

Here’s a practical guide on how to do this using the Protein Path Finder app in SAMSON.

Why setting up conformations matters

The accuracy and success of a conformational transition path search largely depend on how well the initial and final states are defined. If the two conformations are mismatched or incorrectly defined, the computation may fail or give biologically irrelevant results.

Importing models in SAMSON

If you’re following the official tutorial, you can directly download a pre-prepared model of Adenylate Kinase with two conformations by copying the document link here into Home > Download in SAMSON.

Visualizing your conformations

Once downloaded, open the model in the document view. You’ll see two structures representing the 4AKE and 1AKE conformations, typically labeled as start and goal. These represent the open and closed states of the protein’s functional cycle.

Using your own data?

If you plan to use your own conformations from experimental data or molecular simulations, make sure they are provided in the same file, formatted as:

MODEL        1
... (first conformation)
ENDMDL
MODEL        2
... (second conformation)
ENDMDL
END

MODEL 1

... (first conformation)

ENDMDL

MODEL 2

... (second conformation)

ENDMDL

END

This is required so the Protein Path Finder can recognize both conformations properly.

Selecting conformations in Protein Path Finder

Once your document contains the two conformations, launch the Protein Path Finder from Home > Apps > Biology or use the universal search. In the app:

Expand the Set up the system section.
Click Get conformations from the active document.
Select the appropriate models as your Start and Goal conformations.

This will anchor your sampling procedure between two known states of the protein, helping guide the transition path search more efficiently and accurately.

Why it’s worth getting this step right

Defining start and goal conformations correctly ensures that your pathway search remains meaningful biologically and structurally. A well-set system can drastically reduce computation time and avoid unphysical motions or energy instabilities downstream.

Whether you’re studying enzymatic mechanisms, drug-induced conformational changes, or just visualizing flexibility, the ability to set up reliable conformational endpoints forms the critical start line.

To dive deeper into conformational transition modeling and see the full tutorial, visit the documentation page.

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