Deciding whether to delete water molecules when preparing molecular systems for simulations is a challenge many researchers face. While tools can bulk-remove these molecules, knowing which water molecules matter is crucial to preserve the accuracy of your results.
In many crystal structures, water molecules fill the space around proteins, but not all of them are created equal. Some water molecules are loosely bound and far from the active site – these are usually safe to remove. Others, however, are tightly coordinated or play critical roles in enzymatic activity or structural stability. Carelessly deleting all waters may risk omitting such important participants.
Within the GROMACS Wizard Extension in SAMSON, you have precise control over what water molecules to keep or remove. Here is a useful strategy:
Preserving Functional Waters
Let’s say you’re studying the 1AKI protein, which includes important water molecules near its active site. Instead of deleting all waters, you can keep those critical to function and delete others outside this biologically meaningful zone.
Here’s how to do it:
- Select all structural components in the active site – this may include ligands, cofactors, or specific residues and atoms.
- Right-click in the Document view or the Viewport and choose Expand selection > Advanced.
- In the appearing dialog:
- Set node type: Water.
- Condition: beyond a certain distance, e.g., 5 Å from your selection.
- You can use auto-update to preview what’s being selected before making changes.
- Once verified, right-click again and select Erase selection to delete only those waters outside the active site.
This method gives you precision in tailoring your model for simulations and avoids losing key molecules that may influence binding, reaction kinetics, or structural conformations.
Over-deleting or under-deleting waters is a common issue, and this fine-grained approach helps mitigate it. If you’re uncertain about a molecule’s importance, it may be better to keep it and evaluate its role during preliminary simulation analysis.
Tip: Tightly bound water molecules often form hydrogen bonds or coordinate metal ions. Visualization tools in SAMSON can help you identify these cases before deletion.
To learn more and walk through additional steps in system pre-processing (including ligand removal, hydrogen addition, and topology concerns), visit the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at https://www.samson-connect.net.