Water molecules present in crystal structures can either be noise or contribute critically to protein function, especially when located within the active site. As a molecular modeler preparing systems for simulation, one persistent question emerges: how do I remove unnecessary crystal waters while keeping those that matter?
This often becomes a painful manual process, leading to potential oversight or loss of meaningful data. Fortunately, SAMSON’s GROMACS Wizard introduces a workflow that simplifies this challenging step by letting you delete water molecules outside of the active site in a controlled and transparent way.
Why Selective Water Removal Matters
Most simulation pipelines recommend removing crystal waters. However, active-site crystallographic waters are sometimes essential for maintaining structure, mediating interactions, or supporting catalysis. Blind removal can result in poor starting configurations and questionable dynamics.
Instead of guessing which waters to delete, SAMSON lets you define the region that matters — the active site — and erase only the water molecules outside of that range. This balances cleanup with conservation of biochemical detail.
How It Works in SAMSON
Here’s how to selectively remove non-essential waters while preserving functionally important ones:
- Select the active site area, including ligands, residues, or atoms relevant to your system.
- In the Document view or Viewport, right-click and choose: Expand selection > Advanced.
- From the dialog that appears:
- Set Water as the Node type.
- Choose a distance (e.g. 5Å) to include waters beyond your selected region.
- Use auto-update to preview the selection.
- Click OK to confirm water molecules located outside of your active site.
- Finally, right-click this new selection and choose Erase selection.
This keeps your functional region hydated — as determined by crystallography — while excluding water molecules that aren’t essential to your simulation.
When to Use This Method
If your system includes any catalytic, tightly-bound, or coordinative waters (e.g. participating in metal complexes or stabilizing the ligand), this method lets you avoid unintentional deletion. It’s especially useful when working with high-resolution datasets or conserved water networks across protein families.
A Visual Example
The image below shows an example where waters more than 5Å away from a ligand are selected for removal. The operation is performed through an intuitive selection expansion and verification process.
Less Guessing, Better Simulations
This approach improves your model quality without adding much time to the setup process. By using range-based selection with visual feedback, you reduce errors and maintain critical water interactions from crystal structures.
To learn more about preparing your molecular system for simulation with GROMACS Wizard in SAMSON, visit the full preprocessing guide: https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.