Preserving Functional Waters During Preprocessing in GROMACS Wizard

When preparing a biomolecular system for simulation with GROMACS, removing existing crystal waters is often part of the workflow. But not all water molecules are equal—some are tightly bound and participate directly in biochemical function, especially near active sites. Removing them could significantly affect your simulation results. So, how can you remove only the bulk and unimportant crystal waters while preserving essential ones?

In SAMSON’s GROMACS Wizard, you can selectively erase unnecessary water molecules based on their spatial relationship with active site structures. This approach helps maintain simulation accuracy while cleaning up your system efficiently.

Why This Matters

Carelessly deleting all water molecules from a PDB file may lead to undesirable outcomes. Some water molecules form hydrogen bonds crucial for ligand binding or maintain the structural stability of a protein’s active site. Completely removing them can yield unrealistic simulation behavior or require repeating the preprocessing steps.

Thankfully, the GROMACS Wizard in SAMSON offers a spatial selection tool that solves this common problem with a visual and intuitive workflow.

Step-by-Step: Deleting Waters Outside the Active Site

  1. Select key components of the active site, such as residues, ligands, or individually placed water molecules that you know are important. This can be done directly in the Viewport or from the Document view.
  2. Right-click on the current selection and navigate to Expand selection > Advanced.
  3. In the advanced selection dialog box:
    • Set Node type to Water.
    • Choose the beyond distance condition to filter water molecules that lie outside a user-defined cutoff, such as 5Å.
    • Use auto-update to visually preview which molecules will be selected.

    Select waters beyond 5Å

  4. Once you’ve confirmed the appropriate waters are selected, right-click again and choose Erase selection. This step permanently removes only the outer water molecules, leaving behind those you selected to keep near the active site.

Tips and Notes

  • This method is highly flexible—you can change the cutoff value depending on how tightly bound the functional waters are.
  • You can combine this technique with selections based on molecule names or residue IDs for even finer control.
  • Always visually inspect your selection before deletion to avoid accidental removal of important waters.

This approach is especially helpful for systems that come directly from the Protein Data Bank, where water positions are crystallographic and may include both functional and solvent water molecules. By enabling a carefully targeted cleanup, SAMSON’s GROMACS Wizard saves time and avoids unnecessary trial-and-error in system preparation.

To learn more and explore the full preprocessing workflow, visit the GROMACS Wizard – Pre-processing of the system documentation page.

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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