Minimizing the energy of your protein structure is a key prerequisite for accurate conformational path planning — yet it’s commonly overlooked or misunderstood. Whether you’re visualizing transitions between functional states or exploring conformational flexibility, starting from a minimized structure can make or break your results.
In SAMSON, the Protein Path Finder app lets users find possible conformational paths between two protein states using the ART-RRT algorithm. However, before launching any path search, your input model needs to be minimized to ensure reliable energy evaluations and smoother transitions between protein shapes.
Why minimize?
Energy minimization helps relax your protein structure, resolving steric clashes and correcting any unrealistic geometries that might arise from experimental uncertainty or file preparation errors. This stabilized structure ensures that downstream calculations — in particular, energy-based filtering of conformations during sampling — are more physically meaningful.
How to perform energy minimization in SAMSON
To minimize your protein:
- Go to Edit > Minimize in the menu bar.
- Select Universal Force Field (UFF) as the interaction model.
- Click Run to minimize.
UFF is a general-purpose force field designed for a wide range of molecular systems, including proteins. Minimization helps align your simulation closer to the local energy minimum of your selected interaction model, which is important when working with search algorithms like ART-RRT that rely on detecting energy barriers between states.
As shown above, make sure that the correct state updater is also selected — in this case, FIRE (Fast Inertial Relaxation Engine). This method improves convergence speed during minimization by simulating soft ‘nudges’ in geometries, making it well-suited to refining protein structures.
When prompted, accept to use existing bonds in the system. This ensures that the force field operates on a chemically valid input, leveraging the known bonding framework of the protein.
Why FIRE?
FIRE is chosen because of its ability to rapidly reduce energy while maintaining stability. It’s particularly useful when used in combination with constrained minimization approaches applied along the path planning, making it key for both initial preparation and incremental optimization along conformational paths.
Adjusting FIRE parameters like timestep and number of steps further optimizes its performance. In this tutorial, a timestep of 1 fs and step count of 1 was used for constrained minimization during path searches. However, for complete structural minimization before a run, consider increasing the number of steps (e.g., 200-500), to reach a more stable energy minimum.
Before you begin path planning
Minimization shouldn’t be treated as just an optional step. Feeding in a properly minimized structure reduces artifacts during sampling and enables meaningful comparisons between starting and goal conformations. Essentially, it gives your pathfinding algorithm a trustworthy terrain to explore.
You can also export energy information before and after minimization to assess its effect on your structure using the built-in energy windows and graphing tools.
For further steps — such as defining ARAP active atoms or setting up the sampling box — check out the full tutorial. Everything begins, however, with a good energy-minimized foundation.
To learn more, visit the full documentation page here: https://documentation.samson-connect.net/tutorials/protein-path-finder/protein-path-finder/.
SAMSON and all SAMSON Extensions are now free for non-commercial use. This includes the Protein Path Finder app, FIRE, and the interaction models needed for your simulations, making advanced molecular design and simulation more accessible than ever.