When preparing biological systems for molecular dynamics simulations, one recurring pain point is deciding what to do with water molecules. Should you delete all of them? What if some are tightly bound and essential for protein function or ligand binding?
Removing water molecules too aggressively can negatively impact the accuracy of simulations, especially if active-site water plays a structural or catalytic role. On the other hand, leaving all crystal waters from the PDB file may introduce noise and unnecessary complexity. The GROMACS Wizard in SAMSON offers a helpful compromise: a smart way to remove only those waters that are outside the functional regions of your system.
Water selection – the safe way
To remove only the crystal waters that don’t contribute to the key activity of your biomolecule, follow this approach:
- Start by selecting the important structural region: usually the ligand, cofactor, or residues near the active site.
- Right-click your selection in the Document View or Viewport. From the context menu, choose Expand selection > Advanced.
- In the dialog window:
- Set the Node type to Water.
- Select the option for waters beyond a certain distance from your selection — e.g. 5Å or another appropriate value depending on your system.
- Use auto-update to preview the selection and click OK.
- Verify that the correct water molecules have been selected. This step is important to ensure you don’t remove functionally crucial waters by mistake.
- Finally, right-click on the selected waters and choose Erase selection.
This operation is reversible within SAMSON, so you can always reload the structure if you need to retry the selection with a different radius or selection strategy.
Why not delete all water molecules?
Some simulation pipelines default to eliminating all waters during pre-processing, assuming that solvation will be handled later. While valid in many cases, this can be overly simplistic for systems where specific water molecules are mediating hydrogen bonds, stabilizing binding pockets, or participating in reaction mechanisms.
Being selective gives you more control and minimizes the risk of compromising the biological relevance of your model. It’s especially valuable when simulating enzymes or ligand-protein complexes with known structured water molecules in the active site.
Visual aid
The following screenshot shows the SAMSON feature that allows selecting water molecules beyond 5Å from the active site, making it easy to visualize which ones are safe to remove:
Conclusion
In molecular modeling, small details matter, and water is often one of them. With SAMSON’s GROMACS Wizard, you can carefully control your water removal strategy and maintain functionality where it counts. Whether you’re working on enzymatic catalysis or drug binding, this flexible workflow helps reduce manual labor and avoid common mistakes in preparing your simulation systems.
Learn more about how to pre-process systems with the GROMACS Wizard in SAMSON.
SAMSON and all SAMSON Extensions are free for non-commercial use. Visit https://www.samson-connect.net to get SAMSON.