When exploring ligand unbinding pathways in molecular modeling, one common frustration is the unrealistic movement of either the ligand or the protein during simulations. If you’ve found your protein drifting along with the ligand or noticed unnatural trajectories, the problem might lie in the energy setup configuration of your system.
In the SAMSON Ligand Path Finder app, a proper energy model and dynamic updater must be defined before running the ART-RRT algorithm. This article will walk you through the key steps for setting up the Universal Force Field (UFF) and the FIRE (Fast Inertial Relaxation Engine) state updater—two essential components for accurate and stable energy calculations.
Why This Matters
An incorrect or incomplete simulation setup leads to energetically invalid states, unstable paths, and wasted compute cycles. The combination of UFF and FIRE ensures that conformational changes during ligand unbinding are energetically well-evaluated and correctly minimized, allowing you to distinguish between likely and unlikely unbinding routes.
Step 1: Open the Ligand Path Finder App
In SAMSON, navigate to Home > Apps > Biology and open the Ligand Path Finder app. You’ll find a Settings tab where the interaction model and state updater are configured for the upcoming search process.
Step 2: Set Up the Interaction Model and State Updater
Interaction Model: Choose Universal Force Field (UFF) from the dropdown.
State Updater: Select FIRE.
If the FIRE option isn’t visible, make sure the FIRE extension is installed.
Step 3: Configure the Models
When prompted whether to apply a new model, click Yes. For the UFF, select the option to use existing bonds. Two windows will appear:
- A UFF Properties window shows energy parameters for the current model state.
- A FIRE Properties window offers settings for time steps and iterations.
Recommended FIRE parameters:
Step size: 1 fs
Number of steps: 1
Why Use FIRE?
The FIRE algorithm efficiently minimizes energy during system evolution without introducing large perturbations. It’s particularly useful when combined with UFF to maintain a realistic dynamic environment for the ligand and protein.
What You Get
Setting up this energy configuration ensures that the planner runs on a sound energetic foundation. You’ll gain more reliable conformations, better sampling of ligand unbinding paths, and ultimately more biologically relevant insights.
For a complete walkthrough of the Ligand Path Finder setup, including how to define ligands, ARAP atoms, and run the planner, see the full documentation:
Full Ligand Path Finder Tutorial
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.