Crystal Waters in the Way? Here’s How to Remove Just the Right Ones

When preparing a molecular system for simulation, one of the recurring challenges is deciding what to keep and what to discard. And if you’ve worked with PDB files, you’ve likely faced the dilemma around crystallographic water molecules. Do you delete them all? Or leave them untouched, hoping they won’t interfere?

Removing all water might clean up your system—but at the cost of losing functional molecules within the active site. Keeping them all might overload your simulation with unnecessary data. Fortunately, SAMSON’s GROMACS Wizard offers a smart way to surgically remove crystal waters based on their spatial relation to your region of interest.

Why Not Just Remove All Water?

Crystallographic water can play functional roles, especially when tightly bound within active sites of proteins. These molecules may mediate hydrogen bonds or participate in enzymatic mechanisms. Blanket removal, while simpler, could undermine the scientific relevance of your model.

Selectively Removing Crystal Water Outside the Active Site

Here’s a precise way to remove only the irrelevant water molecules with SAMSON:

  1. Select atoms, residues, or structures that make up your protein’s active site—this might include ligands, cofactors, or catalytic residues.
  2. Right-click on the selection in either the Document view or Viewport. In the context menu, navigate to Expand selection > Advanced.
  3. In the dialog box that appears, choose the following:
    • Node type: Water
    • Criterion: Beyond some distance (e.g., 5 Å) from your active site
  4. Use the auto-update option to preview the selection visually. Once satisfied, validate your selection.
  5. Right-click again and select Erase selection to remove only the non-essential water molecules.

Expand selection: select water beyond 5Å

When to Use This Method

This approach is especially useful when you know some waters are functionally important but the rest are noise from crystallographic conditions. Instead of manually checking waters one by one—or risking a simulation bloated with irrelevant molecules—you can make a precise cut in just a few steps.

Going Further

After cleaning your system intelligently, the next steps of parameterization, charge assignment, and solvation become more meaningful and easier to manage. Keeping your model focused on the biology you’re studying saves both CPU time and your own.

Learn more in the original documentation.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.

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