Unexpected distortions in protein simulations can often be traced back to one common oversight: skipping energy minimization before transition path planning. Whether you’re exploring conformational transitions or generating intermediate structures between known states, minimizing your system ensures your results are based on physically reasonable structures from the start.
In molecular modeling workflows using the Protein Path Finder app in SAMSON, this step is required before running the ART-RRT algorithm for exploring conformational transitions. Fortunately, SAMSON offers an easy and quick way to do this using the Universal Force Field (UFF).
What is energy minimization, and why does it matter?
When preparing structures (especially from experimental data like PDB files), coordinates may contain minor clashes or unrealistic bond angles. These issues might seem small, but in simulations, they can multiply into unrealistic transitions or unstable motion predictions.
Energy minimization smooths out these errors by adjusting atom positions to reduce the system’s potential energy. With minimized structures, you’re more likely to obtain meaningful and reproducible transition pathways.
How to minimize your protein in SAMSON
Before launching the Protein Path Finder, go to:
Edit > Minimize
This uses the Universal Force Field (UFF) to quickly minimize your structure. UFF is a general-purpose force field that doesn’t require parameterization and works well for organic and inorganic molecules.
Set up interaction model and state updater
In the Protein Path Finder’s Settings tab, under energy evaluation, assign the minimized structure with:
- Interaction model: Universal Force Field (UFF)
- State updater: FIRE (Fast Inertial Relaxation Engine)
If the FIRE updater is missing, make sure it’s installed from SAMSON Connect.
After selecting these options, SAMSON will prompt you to apply them. Accept the suggested parameters (e.g., use existing bonds) to proceed.
Fine-tuning FIRE parameters
The FIRE Properties window opens, showing the default step size and iteration count. For a light minimization approach suitable for initial screening of paths, set:
- Step size: 1 femtosecond (fs)
- Number of steps: 1
Why minimize before planning?
Even small instabilities—like a single steric clash or unrelaxed side chain—can lead to abnormalities in calculated transition paths. These artifacts might not break your simulation, but they can introduce misleading structures with artificially high energies or disrupt the search process entirely.
Running a quick minimization ensures that you’ve started the path planner on solid ground. It’s a simple step that often makes a big difference.
Further Reading
If you’d like to explore the full path planning process with the Protein Path Finder app, the detailed tutorial walks you through everything—from loading models to exporting paths:
Learn more in the full documentation for the Protein Path Finder app.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.