Understanding how a ligand dissociates from a protein binding pocket is a key question in many areas of molecular modeling and drug design. Once you’ve found potential unbinding paths, the next practical challenge is making sense of them—where does the ligand go? How diverse are the exit routes? What are the energetic challenges along each?
SAMSON’s Ligand Path Finder addresses these questions using a combination of ART-RRT sampling and intuitive path visualization tools. In this post, we focus on viewing and interpreting ligand unbinding trajectories and their corresponding energy landscapes using the Results tab of the Ligand Path Finder app.
Why this matters
While generating ligand unbinding trajectories is important, the ability to compare and inspect the energetic profiles of those paths is just as crucial. Differences in maximum energy barriers, saddle points, or conformational diversity can strongly influence the likelihood of an unbinding route being physiologically relevant.
Exploring the Results Tab
After running simulations in Ligand Path Finder, discovered paths are listed in the Results tab. Each row in the table corresponds to one path, and columns summarize key energetic parameters like:
- MinE: lowest energy in the path (in kcal/mol)
- MaxE: highest energy point
- Saddle: MaxE – MinE
- Barrier: MaxE – First
- Time: how long it took to find this path
This allows users to filter through multiple trajectories by inspecting which paths are smoother, more accessible, or more variable in energy.
Viewing Individual Conformations
Clicking a path in the table reveals its energy curve. A slider appears, allowing step-by-step navigation through the conformations along the path. Moving the slider updates the 3D model, showing how the ligand exits the binding pocket.
This is a powerful way to link energy changes with structural conformations of both the ligand and the protein. For example, sharp upward energy transitions might correspond to the ligand squeezing through tight bottlenecks, which you can observe visually in the model.
Compare Multiple Paths
Use Ctrl (or Cmd on Mac) to select multiple paths and compare their energy profiles side by side. This helps highlight which paths may be energetically more favorable or which show smoother transitions. Visualization assists in identifying potential alternative exit routes – valuable for understanding escape mechanisms or rationalizing mutations at the binding site.
Exporting and Sharing
Export tools allow copying path table content, extracting energies, exporting full paths as trajectories, or saving selected conformations into the main SAMSON document. This makes it easy to include path visualizations in presentations, share with collaborators, or refine further using tools like P-NEB.
Final Thoughts
When working with molecular pathways, analysis is just as important as computation. The Ligand Path Finder not only generates potential unbinding routes, but also equips you with tools to visually interpret and evaluate them using structural and energetic information. This makes it easier to decide which paths merit further analysis, possibly guiding next steps in rational drug design or molecular engineering tasks.
To learn more about using the Ligand Path Finder and visualizing unbinding paths, visit the original tutorial at https://documentation.samson-connect.net/tutorials/ligand-path-finder/ligand-path-finder/.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.