When exploring conformational transitions in proteins, it’s tempting to dive straight into sampling and path search. But many molecular modelers have encountered a frustrating issue: unrealistic or noisy paths that seem physically implausible. A common cause? Skipping proper energy setup before running the search.
In this post, we’ll take a closer look at the importance of configuring energy evaluation before using SAMSON’s Protein Path Finder app—and how to do it properly.
Why energy evaluation setup is critical 🔍
The Protein Path Finder app relies on energetic information to guide the search for conformational pathways. If the energy model is missing or badly defined, path planning may optimize irrelevant properties or introduce artefacts. More importantly, results may not reflect physically realistic motions.
Before launching the search, it’s essential to:
- Define how atoms interact via an appropriate interaction model
- Select a proper state updater to guide the system through small energy-optimized deformations
Setting up energy evaluation in SAMSON
Here’s how to properly set up energy evaluation in the Protein Path Finder app using the Universal Force Field (UFF) and the FIRE minimizer:
- Go to the Settings tab of the Protein Path Finder app.
- From the dropdown, choose Universal Force Field (UFF) as the Interaction model.
- Choose FIRE (Fast Inertial Relaxation Engine) as the State updater. If you don’t see it, make sure it’s installed (check out the app here: FIRE).
- A window will prompt you to apply this new model—click Yes.
- When asked whether to use existing bonds, confirm by selecting this option and click OK.
This will bring up two windows: one for UFF settings and another for FIRE. Adjust the FIRE parameters as shown below:
- Step size: 1 fs
- Number of steps: 1
Here’s the visual reference for this setup 👇
Does the system need to be minimized?
Yes. Before running the planner, make sure your system has been minimized. Use Edit > Minimize in SAMSON to perform geometry minimization based on UFF.
Skipping this can result in non-physical conformations that bias the final path or exaggerate energy differences along the trajectory.
What happens if energy isn’t set up?
If no interaction model is defined, or the state updater isn’t properly configured, the path search might proceed without any realistic energy constraints. The resulting paths may still look smooth but can include physically inaccessible states or introduce distortions that make your analysis invalid.
Tip: Reuse minimal setups
If you’re running multiple path searches for a series of similar systems, setting up a consistent energy evaluation procedure using scripts or templates can save time and improve reproducibility.
By ensuring proper energy setup, you’re not only improving the scientific validity of your results—you’re also preventing wasted compute time on unrealistic conformational searches.
Learn more by visiting the full tutorial for the Protein Path Finder.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON from https://www.samson-connect.net.