When preparing a biomolecular system for simulation, one common challenge is deciding how to handle water molecules. This can be especially tricky if you want to remove excess solvent but preserve functionally important active-site waters. Removing all crystal waters by default might lead to unrealistic simulations, especially if bound water plays a catalytic or structural role.
The GROMACS Wizard in SAMSON provides intuitive tools to manage this, offering a precise method to selectively delete water molecules only outside of the active site. Here’s how you can achieve this with minimal effort.
Why Not Just Remove All Water?
Bulk water is often removed during pre-processing to avoid conflicts during solvation, but not all water molecules are the same. Some are tightly bound and play essential roles in maintaining protein structure or acting as intermediates during catalysis. It’s important to keep these during simulation, but identifying them manually can be tedious.
Let’s walk through how SAMSON’s GROMACS Wizard lets you automate and verify water selection based on spatial context.
Step-by-Step: Delete Water Outside the Active Site
- Select key structures in the active site: Start by selecting the ligand, residues, or water molecules that make up the active site in the Document view or Viewport.
- Expand the selection: Right-click your selection and navigate to Expand selection > Advanced. This opens a dialog allowing spatial filtering.
- Filter water beyond distance: In the dialog, set Node type to Water and choose a distance value (e.g., 5 Å) for filtering. Click Auto-update to visualize the selection and make adjustments. Once satisfied, click OK.
- Delete selected water molecules: Right-click the newly selected water molecules and use Erase selection to remove them.
This process ensures that only waters outside a defined sphere around the active site are removed, preserving those that interact functionally with residues or ligands.
Visual Example
Here’s what the selection looks like when set to find water molecules beyond 5 Å from the active site. This visual feedback helps confirm you’re not removing too much (or too little):
Things to Keep in Mind
- If the protein-ligand interaction is dependent on structured water, always double-check before deleting.
- This method works best when your active site is clearly defined in your selection.
- After deleting, inspect again visually to make sure no unexpected water molecules were removed.
Want to dive deeper into system pre-processing in SAMSON? You can read more in the original documentation, including loading molecules and removing ions, ligands, and alternate atom locations: GROMACS Wizard – Pre-processing of the System.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.