When modeling conformational transitions in proteins, small details can lead to big differences in results. One frequently overlooked step is proper energy minimization before running any transition pathway planning. Skipping this step can introduce artificial forces, limit convergence, or worse — produce physically unrealistic transitions.
This post walks you through how to correctly minimize a protein structure using the Universal Force Field (UFF) in SAMSON — helping ensure smoother and more realistic conformational searches later, for example with the Protein Path Finder app.
Why minimize the structure first?
When proteins are imported from experimental data (e.g. PDB files), they often contain steric clashes, unrealistic bond geometries or missing hydrogen atoms. Running conformational transition algorithms with such input may steer results away from biologically relevant pathways. A geometry and energy minimization step helps start your computations on a more stable baseline.
How to perform energy minimization in SAMSON
Start by ensuring you have loaded your system properly, either as a SAMSON document or directly as a PDB file via the Home > Download menu.
Then follow these steps to minimize the system:
- Go to Edit > Minimize.
- In the minimization dialog, select Universal Force Field (UFF) as your interaction model.
- Use an appropriate state updater such as FIRE (Fast Inertial Relaxation Engine). If you haven’t installed it yet, you can get it from SAMSON Connect.
After launching the minimization, SAMSON may prompt:
- Apply a new model? Choose
Yes. - Use existing bonds? Choose to use existing bonds and click
OK.
Two new windows open:
- The UFF Properties window shows the current force field parameters and the system’s energy.
- The FIRE Properties window lists optimization settings.
For a quick minimization useful before transition planning, set these FIRE parameters:
- Step size: 1 fs
- Number of steps: 1
This will apply a minimal adjustment sufficient for transition tools such as ART-RRT to operate under more physically reasonable boundary conditions.
How this helps with conformational paths
After minimization, you’re ready to explore conformational pathways more reliably. Tools like the Protein Path Finder use this minimized structure as a base state. Starting from a well-relaxed configuration increases the realism of sampled trajectories and reduces convergence time.
If you’re working with two different conformations (start and goal), make sure both are separately minimized and then merged into a single multi-model PDB file or a SAMSON document.
Documentation reference and links
To explore the full tutorial, scenarios, and additional steps for running protein conformational transitions with the ART-RRT method, visit the official documentation page:
https://documentation.samson-connect.net/tutorials/protein-path-finder/protein-path-finder/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.