When preparing molecular systems for simulation using GROMACS, one of the first steps is to remove unnecessary components like water molecules. However, a common concern for molecular modelers is accidentally deleting functional or tightly bound crystal waters from the active site. These water molecules may be critical for the structural integrity or catalytic mechanism of a protein, and their removal could significantly alter the results of a simulation.
The GROMACS Wizard in SAMSON offers an elegant, visual way to selectively delete only the unwanted water molecules — making this step easier and less error-prone.
Why this matters 🔍
Not all water is created equal. In PDB structures, some water molecules are simply bulk solvent — their positions captured under crystallographic conditions — while others are tightly bound, sometimes even mediating interactions in the active site or participating in catalysis. Removing all waters without discrimination can lead to unrealistic simulation conditions, especially around the protein’s functional core.
How to selectively delete external water
Fortunately, the GROMACS Wizard in SAMSON lets you handle this with a thoughtful selection procedure:
- Select the active site elements (e.g., ligand, cofactors, or protein residues) either in the Document view or directly in the Viewport.
- Right-click the selection and choose Expand selection > Advanced. A dialog box will appear allowing you to define a selection rule.
- Set the Node type to Water, and select water molecules beyond a certain distance — typically 5 or more Angstroms — from your active site. You can enable auto-update to preview what will be selected before applying the filter.
- Verify the selection visually. This is crucial to ensure functional waters near the active site are preserved.
- Erase the selected waters using the right-click menu.
This method ensures you retain critical localized waters while decluttering the simulation system from unnecessary ones.
Best practices
- When in doubt, cross-reference literature or structural studies describing the importance of observed water molecules.
- If a water molecule has multiple hydrogen bonds with active site residues or ligands, it might be functional.
- You can build an initial system both with and without certain waters, and test their influence through short simulations.
Selective water deletion can go a long way in improving the biological relevance and stability of your simulations. The GROMACS Wizard in SAMSON allows you to do this with a clear and visual workflow, reducing the chance of mistakes often made with command-line based tools.
To learn more and access the full documentation, visit the Pre-processing section of the GROMACS Wizard tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.