When preparing biomolecular systems for molecular dynamics simulations with GROMACS, one common but confusing step is deciding what to do with crystal water molecules. Should all crystallographic water be deleted? What if some are essential to the protein’s function? This is a frequent challenge, especially for those simulating enzyme-ligand complexes or binding pockets where water might play a key structural or functional role.
If you remove too much water, you risk losing valuable interactions. But if you remove too little, your system might not be physically realistic. The GROMACS Wizard in SAMSON helps strike that balance with an interactive way to clean up crystal waters based on spatial proximity.
Selective Water Deletion Based on Distance
Instead of bluntly deleting all water molecules before solvation, SAMSON users can follow a simple workflow to remove only the unimportant ones — those that don’t participate in critical interactions — while keeping structurally important water molecules present in the active site.
Here’s how it works:
- Select key structures like ligand atoms, important residues, or anything within the active site.
- Right-click the selection in the Document View or the Viewport and choose Expand selection > Advanced.
- In the dialog that appears, choose Node type: Water, and set a condition like
beyond 5 Åto target water molecules far from the selection. - Enable the Auto-update option to preview the affected waters before applying.
- Once verified, right-click on the selection again and choose Erase selection.
This approach lets you delete just the water you don’t need—reducing system complexity while keeping biologically relevant structural waters intact. The method is flexible, and you can experiment with different distance thresholds depending on how tightly bound water clusters are within your system.
Why This Matters
Water molecules seen in crystal structures aren’t all created equal. Some are experimental artifacts, weakly coordinated or part of evaporation buffers, while others are essential for active site geometry or stabilizing hydrogen bond networks.
Blindly deleting all waters can disrupt simulation results, especially when comparing the flexibility of a ligand in bound and unbound states. That’s why this more nuanced method can improve your simulation fidelity without a complicated script.
To learn more about pre-processing systems using GROMACS Wizard in SAMSON, including how to load PDBs, remove ligands, and parameterize arbitrary molecules, visit the full documentation here: https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.