Why You Might Not Want to Delete All Waters in Your Molecular System

When preparing a protein structure for simulation, one frequently encounters the question: should I delete all the water molecules from the structure? Many molecular modelers default to removing all crystal water molecules at the preprocessing stage, but in some cases, this can compromise simulation accuracy.

In GROMACS Wizard for SAMSON, part of the preprocessing workflow includes an option to “Remove water”. This is generally helpful for removing non-essential solvent, but this step requires additional caution: some waters within the system might play structural or functional roles, especially if they are tightly bound or located in the active site of a biomolecule.

Why preserve some water molecules?

In X-ray crystallography data, water molecules identified in the structure may either be structurally important, help stabilize active sites, or mediate interactions between protein residues and ligands. Simply deleting all water molecules before simulation can inadvertently remove these crucial participants.

Selective deletion: a better approach

With SAMSON’s GROMACS Wizard, you can use a more fine-grained approach by removing only the waters that are not near your region of interest, such as the active site. Here’s how you can selectively delete water molecules farther than a given distance from your selection (e.g. a ligand).

  1. Select the region of interest, such as ligand atoms or key residues near the active site.
  2. Right-click on the selection in either the Document view or the Viewport.
  3. In the context menu, choose Expand selection > Advanced.
  4. In the pop-up dialog:
    • Set Node type to Water.
    • Set the condition to select waters beyond a specific distance (e.g., 5 Å) from your initial selection.
    • You may use the auto-update checkbox to preview your selection visually.
  5. Click OK to apply the selection.
  6. Right-click on selected water molecules and choose Erase selection.

This targeted method lets you keep the waters that matter most while cleaning up noise in the structure. It’s especially useful when preparing systems that include cofactors, metal ions, or multi-chain complexes where water often plays a bridging or stabilizing role.

Expand selection: select water beyond 5A

Tip: If you’re unsure whether a water molecule is functionally relevant, look for literature on your system (e.g., PDB entry annotations or publications) that might describe the role of conserved waters.

Taking a few minutes to clean your system with care can help avoid missing key interactions or introducing instability into your simulation. Small steps like this can make a big difference in the quality of your results.

To explore more details about this preprocessing step in SAMSON’s GROMACS Wizard, read the official documentation.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at www.samson-connect.net.

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