Preparing for a ligand unbinding simulation in molecular modeling isn’t just about running an algorithm—it’s about setting up your system correctly so that the underlying method can do its job properly. One of the most important steps, often underestimated, is defining which atoms belong to the ligand.
In SAMSON’s Ligand Path Finder, this precise step can have a significant impact on how realistic or interpretable your results are. And the good news is: it’s easy to get right, once you know what to look for.
One common issue that arises in interactive molecular modeling is with the selection of ligand atoms. For many users, especially those unfamiliar with SAMSON, the temptation is to simply select a visible portion of the molecule in the viewport. However, this can lead to ignored or misassigned atoms that should be treated as part of the ligand, resulting in flawed simulations.
How to Properly Select Ligand Atoms
In SAMSON, ligand atoms are selected via the Document view, which lists all the components—proteins, ligands, residues, and more—in a convenient tree structure.
To ensure full and accurate selection of your ligand atoms, follow these steps:
- Locate the ligand structure in the Document view. In the official tutorial, the ligand is
TDG(Thiodigalactosid). - Click on
TDGto select all atoms belonging to the ligand. - Once the ligand is selected, click the Set button in the Ligand Path Finder app to assign the selection as ligand atoms.
By doing this, SAMSON internally distinguishes the ligand from the rest of the molecular system (typically the protein), allowing the ARAP and RRT algorithms to treat it as a mobile unit within the unbinding pathway search.
Tip: Once you’ve assigned the ligand atoms, the Advanced information box will show how many atoms are designated as part of the ligand. This is a great verification step to make sure nothing was accidentally skipped.
Why Does This Matter?
ARAP (As-Rigid-As-Possible) modeling handles ligand motion by dividing the atoms into active and passive categories. But this only works correctly if the software knows which atoms are part of the ligand in the first place.
If a ligand atom is accidentally left unassigned, or a protein atom mistakenly included as part of the ligand, it can skew the results. You may see unrealistic unbinding pathways or high-energy artifacts that would be avoided with proper setup.
Tip for larger ligands: If you’re working with complex, branched ligands, consider using SAMSON’s group tools to predefine your ligand selections in organized groups. This helps reduce confusion and ensures repeatability across simulation runs.
Make the Setup Repeatable
Another helpful feature built into this workflow: if you’re not happy with your selection, you can easily reset it. Just click the Reset button next to the ligand atom setup. This makes experimentation and parameter tweaking much less risky.
Getting this part of the setup right may seem minor at first, but it plays a foundational role in generating reliable, interpretable unbinding simulations. Whether you’re interested in pathway exploration, drug target analysis, or basic docking refinement, ensuring you’ve correctly defined your ligand gives you a strong starting point.
To learn more or go through the full tutorial interactively, visit the official documentation page for Ligand Path Finder.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at www.samson-connect.net.