When preparing a biomolecular system for simulation, one common step is removing unnecessary water molecules. But not all waters are created equal. Active-site waters, often tightly bound and functionally important, should typically be preserved. So how can you remove only the crystal waters that are not involved in the core biological function of the system?
If you’re using the GROMACS Wizard in SAMSON, there’s a precise and intuitive way to accomplish this.
Why This Matters
Simulations that include irrelevant water molecules can become unnecessarily large and slow. Worse, removing relevant water molecules—such as structural or catalytic waters—can impact the biological accuracy of your simulation results. Balancing the need for computational efficiency with chemical realism is a challenge many molecular modelers face, especially when working with PDB files that often contain hundreds of crystal water molecules.
Selecting and Deleting Only the Unwanted Waters
The Expand Selection > Advanced tool in SAMSON offers a distance-based filtering approach to remove only those waters that lie beyond a defined region of interest. Here’s how:
- Select your region of interest. Choose atoms, residues, or molecules that define your active site (e.g., a bound ligand, critical residues, or known active-site waters).
- Access advanced selection settings. Right-click on your active site selection in the Document view or Viewport, then choose Expand selection > Advanced.
- Set your criteria. In the pop-up dialog:
- Select Water as the node type.
- Choose the option beyond a certain distance from the current selection (e.g., 5 Å).
- Enable auto-update to preview your selection.
This dynamically selects only waters lying outside your region of interest.
- Delete the selected water molecules. After verifying your selection, right-click on it and choose Erase selection.
Tips for Better Results
- This method can be combined with visual inspection to avoid removing structural waters that might not be part of your ligand binding site but still contribute to protein stability.
- Consider combining this with the Document view’s hierarchy to double-check what has been selected before erasing anything.
- If you’re unsure, save a copy of your structure beforehand—SAMSON allows you to easily go back to previous steps.
When to Use This
This approach is ideal when working on:
- Ligand-binding simulations where you need accurate electrostatics and don’t want extra waters skewing results.
- MD simulations where efficiency is a priority, and large numbers of water molecules slow down computation.
- Systems where certain internal waters mediate hydrogen bonding networks and must be retained for functional simulations.
This targeted removal method helps you strike the right balance between biological relevance and computational efficiency.
To explore this functionality in more detail or discover additional workflow steps, check out the original documentation page: 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.