When searching for protein conformational transition paths, one of the most common frustrations for molecular modelers is running simulations that are unstable, inaccurate, or—worse—fail to converge entirely. If your ART-RRT runs in SAMSON aren’t giving reliable results, the culprit might be simpler than you think: the initial energy minimization setup.
In this post, we’ll walk through why preparing your system with the proper interaction model and state updater in Protein Path Finder is critical before you run the simulation. If you’re skipping or rushing this step, it’s time to fix that. 🧪
Why You Need Energy Minimization
Before launching any conformational path search, you must make sure the system is properly minimized. Without this, any small clash or irregular bond length can ruin the simulation outcomes or bias the planner unfairly. SAMSON makes this easier with the built-in Edit > Minimize function, which applies the UFF (Universal Force Field).
How to Set It Up Correctly in Protein Path Finder
When using the Protein Path Finder app, once your structure is loaded, head into the Settings tab. This is where key decisions are made for how your simulation will behave.
Interaction model: Choose Universal Force Field (UFF) from the dropdown. UFF supports all elements and is general-purpose—perfect for broad modeling scenarios.
State updater: Select FIRE (Fast Inertial Relaxation Engine). This is a robust minimization method that quickly reduces energy using damping dynamics. If you don’t see FIRE listed, make sure it’s installed from SAMSON Connect.
Once selected, you’ll be prompted to confirm the new interaction model and asked whether to use existing bonds—choose to keep existing bonds. Then, two new windows will appear: one for UFF energies, and one for FIRE parameters.
Set the FIRE step size to 1 fs and the Number of steps to 1. These low values allow precise updates during minimization for each conformational step.
Why This Matters
Misconfigured interaction models and minimization settings are a silent killer of trajectory quality. By automatic default, results might seem ‘good enough’ but can hide unrealistic energies or distorted geometries. Taking 1–2 minutes to assign appropriate force fields and optimizers is the kind of detail that separates patchy results from publication-ready simulations.
Before You Hit Run…
If you only remember one thing from this post: don’t skip or auto-confirm default energy settings. Instead, double-check that you’ve set UFF and FIRE, minimized the current conformation, and tuned FIRE options. Only then are you ready to start defining the path planning parameters.
To explore the full setup and learn how to configure the rest of the Protein Path Finder workflow—from setting active atoms to exporting final trajectories—visit the full documentation here: Protein Path Finder tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.