When setting up molecular dynamics simulations, one common challenge is deciding what to keep and what to remove from crystallographic structures. Crystal water molecules, for instance, can be tightly bound in the active site or loosely attached elsewhere in the structure. Removing all waters might simplify the system—but it could also compromise accuracy if functional water molecules are deleted.
Fortunately, in the SAMSON GROMACS Wizard, there’s a helpful workflow that lets you selectively delete crystal waters only outside the active site. This simple yet powerful feature can save hours of manual editing and reduce the risk of mistakenly erasing important molecules.
Why delete some waters—but not all?
Protein structures from the Protein Data Bank often include numerous waters. While many of them are artifacts of crystallization, some are essential: they form hydrogen bonds in the active site or stabilize interactions. Deleting these indiscriminately could disrupt your simulation. Conversely, keeping all water molecules may unnecessarily increase computational cost and simulation complexity. The goal is to smartly simplify the system while preserving what’s functionally relevant.
How to remove only non-essential waters in SAMSON
To remove water molecules located outside of your protein’s active site, follow these steps in the GROMACS Wizard:
- Select atoms or residues in the active site (e.g., the ligand, catalytic residues, or any known binding molecule).
- Right-click on the selected region in the Document view or Viewport.
- Navigate to Expand selection > Advanced.
- In the pop-up dialog, set the Node type to Water, and configure the filter to include waters located beyond a certain distance (e.g., 5Å) from your selection. Use the auto-update checkbox to preview in real time.
- Once you’re satisfied with the selection, press OK.
- Finally, right-click the selected water molecules in the Document view or Viewport and choose Erase selection.
This method allows you to preserve waters near the active site—especially vital for systems with known functional water molecules—while discarding distant waters that are unlikely to contribute meaningfully to the simulation.
When is this approach especially useful?
- When working with metalloproteins or enzyme-ligand complexes where water mediates interactions.
- In ligand binding studies that depend on key bridging waters.
- While creating minimal systems to reduce simulation size.
This targeted approach lets you balance biological realism with computational efficiency.
To learn more about system pre-processing in the GROMACS Wizard, visit the full tutorial at this documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.