Cleaning Up Water Molecules Without Losing Functional Waters

In molecular simulations, especially when preparing systems using GROMACS, it’s common to remove water molecules from the initial structure to avoid unwanted interactions or duplicate solvation. However, researchers often face a recurring dilemma: how can you quickly remove unnecessary crystal water molecules without deleting the functional ones found in the active site?

This is especially relevant when dealing with PDB files downloaded from the Protein Data Bank, where water molecules may be scattered throughout the structure. While many can be safely discarded, some waters may participate in essential biological interactions—such as hydrogen bonding in binding pockets—and should not be removed lightly.

SAMSON’s GROMACS Wizard provides a powerful and user-friendly way to selectively delete crystal water molecules based on their spatial relationship to the active site. Using the advanced selection tools, you can identify and erase only those water molecules that lie beyond a defined distance from your region of interest.

Identify and Preserve Critical Waters in SAMSON

Here’s a step-by-step approach you can use directly from the GROMACS Wizard documentation to clean up water intelligently:

  1. Select active-site components: Identify the atoms, residues, ligands, or functional groups that define the active site of your protein. Select them using the Viewport or Document view.
  2. Expand the selection: Right-click the current selection and navigate to Expand selection > Advanced.
  3. Configure the expansion: In the popup dialog, choose Water as the node type, set the distance to define your active-site boundary (e.g., 5 Å), and enable auto-update to preview the selection.
  4. Verify the selection: Make sure only the water molecules outside of the binding pocket are selected. Visual feedback helps ensure meaningful cleanup without data loss.
  5. Erase the external waters: Right-click the selection again and choose Erase selection to clean up the unnecessary waters.

This method helps retain biologically meaningful interactions while pruning redundant solvent molecules, especially beneficial if you’re feeding the system into solvation or topology generation pipelines.

Expand selection: select water beyond 5A

You’ll especially appreciate this approach if your structure contains tightly bound waters that participate in ligand recognition or maintain protein conformation. It offers a better alternative to the blunt strategy of removing all water, a common shortcut that often goes unnoticed and can affect simulation outcomes.

This feature is part of the Pre-processing stage in the GROMACS Wizard workflow in SAMSON. For additional context and detailed instructions, visit the original documentation page: 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.

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