One common challenge in molecular modeling is creating meaningful transition pathways between two conformations of a protein. Whether you’re studying allosteric mechanisms, conformational flexibility, or receptor–ligand induced fit, identifying and selecting the correct starting and target shapes can be one of the most time-consuming steps.
If you’re using SAMSON, the Protein Path Finder app helps simplify this crucial task. This post walks you through how to effectively choose your start and goal conformations within the app, a necessary step before running any protein transition simulations.
Why conformation selection is important
Transition paths are generated between two known structures—a starting point and a target. For meaningful results, these conformations must be accurate, clean (minimal artifacts), and biologically relevant. Choosing the wrong conformations can skew your pathway results, making your downstream analysis harder.
Step-by-step: Selecting Conformations
Once you’ve loaded your document in SAMSON that contains two models—typically the experimental structures of a protein in two states—you need to define which model is your start and which one is your goal within the Protein Path Finder interface.
- Open Protein Path Finder via Home > Apps > Biology, or find it using the Find everything search bar.
- In the Settings tab, click “Get conformations from the active document”. This will list the conformations (models) available in your loaded protein structure file.
- From the dropdown lists, assign the correct model as your Start conformation, and your desired final structure as the Goal conformation.
That’s it — you’ve now seeded the search process with your conformational boundary conditions.
Tips and things to keep in mind
- Ensure your file has both conformations integrated as separate models (MODEL 1, MODEL 2) in a single document.
- If you’re preparing your own input models, make sure the protein has identical topology (same residues, atoms, etc.). Use SAMSON’s PDBFixer or Protein Preparation & Validation tools for structure cleanup.
- One good practice is to visually inspect the structures before proceeding. Confirm that the movement you’re interested in is captured meaningfully between the two states.
This selection step can save hours of debugging, especially if the conformation data isn’t consistent. It also sets the stage for successful downstream processing, like motion planning with RRT algorithms or refinement using methods like P-NEB.
Efficiency without scripting
What’s nice is that all of this can be done inside the SAMSON GUI, with no need for scripting. For those just getting into molecular modeling, or who are working on tight deadlines, having a point-and-click interface that lets you select conformations quickly is a real timesaver.
To explore how to generate accurate transition pathways after selecting your conformations, refer to the full tutorial here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON here.