Before jumping into docking simulations, there’s one crucial step that experienced molecular modelers know better than to skip: system preparation. While it might feel like a formality, not preparing your protein structures correctly can lead to misleading results or failed calculations down the line. Here’s a closer look at why preparation matters and how to get it right using the Hex Extension in SAMSON.
Why preparation matters
PDB files from structural databases often contain artifacts and elements that aren’t relevant—or worse, detrimental—to docking calculations. Water molecules, monatomic ions, alternate atom locations, or missing hydrogens can skew electrostatic potentials, affect steric clashes, or disrupt scoring functions.
If your docking results don’t align with expectations, improper structure preparation is often the invisible culprit.
Preparation basics: the checklist
In the Hex tutorial, SAMSON streamlines this crucial stage. Here are the essential steps you can perform directly within the app:
- Remove alternate atom locations – ensures a single conformation per residue.
- Remove water, ions, and ligands – unless functionally relevant, these can be removed to simplify the system.
- Add hydrogens – particularly important for electrostatics-based scoring.
Fortunately, you don’t have to do this manually 🙌. SAMSON groups all these options under Home > Prepare. You can toggle each option based on your needs and apply them in one go:
What if the structure has missing atoms?
If your protein structure is incomplete—missing residues or side chain atoms—you can use the PDBFixer Extension. This tool fills in gaps in the molecular structure and can even add hydrogens at a defined pH. It’s incredibly helpful when working with low-resolution data or homology models.
Visualize smart
After prep, a visual check can go a long way. In Document view, you can switch on the ribbon model of the protein to examine secondary structure. SAMSON makes this easy through:
Visualization > Visual model > Ribbons
If you don’t see the Document view, enable it from the menu or hit Ctrl/Cmd + 1.
A tip on post-preparation confidence
For peace of mind, it’s worth matching your prepped system back to your intended input. Is the binding site preserved? Are ligands correctly removed (or retained)? Are hydrogens distributed as expected? A few moments of review can save hours later when interpreting results.
When preparation is already done
Bonus: If you’re using the SAMSON tutorial sample file, the system comes pre-cleaned. Water is removed and hydrogens are already added. But knowing how to do it is what sets casual users apart from professionals.
Learn more about protein docking with the Hex Extension in SAMSON.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.