One of the subtle yet recurring challenges in preparing biomolecular systems for simulations is the question of what to do with crystal waters. These water molecules, often captured in PDB structures, can be either essential to the biological function or irrelevant bulk solvent.
Removing all water molecules indiscriminately during pre-processing can lead to a simulation setup that lacks critical interactions, especially when tightly-bound waters are involved in the active site. Conversely, retaining too many can complicate the system and slow down simulation performance unnecessarily.
To address this, the GROMACS Wizard in SAMSON provides a targeted approach for selectively removing water molecules outside the active site — offering fine control with minimal effort. If you’ve ever found yourself wondering how to selectively clean your system without manually inspecting every water molecule, this guide might be just what you need.
Step-by-step: Delete only the waters you don’t need
This workflow is intended for situations where your system contains tightly-bound water molecules (e.g., hydrogen-bonded to a ligand or protein active site), and you want to retain them while deleting all other crystal waters.
- Select the active site components.
Select structures such as the ligand, nearby residues, or known functional water molecules either in the Document view or directly in the Viewport. - Expand the selection.
Right-click your selection and go to Expand selection > Advanced. - Target nearby waters.
In the dialog that appears:- Set the Node type to Water.
- Choose the option beyond a specified distance (e.g., 5 Å) from your original selection.
- Enable auto-update to visualize which water molecules are being selected dynamically.
Verify that only waters outside the active site are selected.
- Erase selection.
Once satisfied, right-click on the selected waters and choose Erase selection to remove them.
Why this workflow helps
This approach offers molecular modelers a reproducible, visual method for curating water molecules intelligently. You avoid removing critical waters that could affect active site dynamics while cleaning out unneeded molecules that might otherwise clutter your simulation box or artificially influence thermodynamics.
Because the selection is dynamic and visual, it removes much of the guesswork and manual setup often required when fine-tuning input structures for simulations. It also integrates seamlessly with other features in SAMSON’s GROMACS Wizard, like ligand removal and hydrogen addition.
If you’re designing simulations where accuracy of the active site environment is crucial — such as enzyme kinetics, ligand binding studies, or virtual screening preparation — this step will ensure you’re working with a biological system that’s both accurate and efficient.
To explore this and other related features, visit the full documentation page:
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.