Anyone working with biomolecular simulations knows the drill: you fetch a structure from the Protein Data Bank and it comes with water molecules — hundreds of them, sometimes thousands. The big question is: which ones should you keep?
In many cases, you’ll want to delete crystal water molecules before running your simulation, especially when preparing a system for molecular dynamics with tools like GROMACS. But not all waters are simply background noise. Some, especially those in or near active sites, play functional roles, stabilize protein folds, or mediate essential interactions.
The GROMACS Wizard in SAMSON offers a targeted way to handle this: it lets you easily erase only the unwanted crystal waters — those outside active sites — and keep the important ones. Here’s how it works, and why it matters.
Why not just remove all waters?
It might feel tempting to wipe the slate clean. After all, GROMACS can solvate your system later. But blindly removing all crystal waters can be a mistake if certain water molecules are tightly bound, or functionally important — often referred to as “structural waters.”
Fortunately, SAMSON gives you the best of both worlds: control and automation. Here’s how to selectively delete water molecules outside of functional regions in the GROMACS Wizard pre-processing workflow.
The Procedure
- Select the active site:
In the Document view or Viewport, select elements of the active site (ligand, retained waters, residues, cofactors, etc.). This anchors the region you want to preserve. - Expand the selection:
Right-click the current selection and navigate to Expand selection > Advanced. - Define a distance criterion:
In the popup, select Water as the Node type. Choose a condition like beyond 5 Å from the current selection. Turn on auto-update to preview your selection and fine-tune the distance if needed. - Delete the excess water:
Confirm the selection and right-click in the Viewport again to select Erase selection.
That’s it — the waters outside your defined distance are removed, leaving behind only those in or near the active site. You now have a clean, focused system ready for further preparation and simulation.
When should you use this?
- If your active site includes water-mediated hydrogen bonds
- If you plan to analyze conserved water positions across structures
- When running simulations on protein-ligand or enzyme-substrate complexes
This approach is particularly valuable in drug design and enzymology, where every interaction counts. Removing only non-functional waters ensures simulation consistency while maintaining biological relevance.
For more details and step-by-step instructions, refer to the official documentation:
https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON from https://www.samson-connect.net.