One of the subtle but crucial steps in preparing a biomolecular system for simulation is deciding which water molecules to keep and which to remove. This is especially true when setting up systems for GROMACS simulations, where unnecessary crystal waters can interfere with energy minimization or MD runs—but deleting all waters blindly could eliminate structurally important ones near the active site.
In many PDB structures, water molecules are abundant and not all of them are functionally relevant. Still, manually selecting waters to remove can be error-prone and time-consuming. Fortunately, SAMSON’s GROMACS Wizard provides a convenient way to streamline this step, helping molecular modelers strike the balance between cleaning up the system and preserving functionally relevant waters. 💧
Why It Matters
Some water molecules in macromolecular structures form part of ligand binding pockets or are involved in hydrogen bonding networks stabilizing conformations. Automatically deleting all waters may lead to inaccurate simulations. At the same time, retaining all waters inflates system size and can cause errors in downstream GROMACS steps. The pain point? Deciding which waters to remove—efficiently and safely.
The Solution: Targeted Water Removal with Distance-Based Selection
The GROMACS Wizard in SAMSON includes an advanced selection feature that lets you precisely keep or remove water molecules based on their distance from key regions, such as the active site.
Here’s how you can do it:
- Select a reference point in the structure—this could be the ligand, a cofactor, or active site residues.
- Expand the selection using Expand selection > Advanced from the context menu in either the Document view or Viewport.
- In the dialog window, set the Node type to
Water. Choose a distance beyond which you want water molecules to be selected (e.g. 5Å beyond the active site). - Enable auto-update to visually preview the selection.
- Click OK when you’re satisfied, then right-click the selection again and choose Erase selection.
This selective method ensures that tightly bound or structurally important waters near the active site remain, while the bulk solvent can be removed to create a cleaner and more simulation-ready system.
When Should You Use This?
This method is particularly useful:
- When preparing protein-ligand complexes for drug design or screening.
- If the system contains crystallographic waters in binding pockets.
- When you want to minimize the system size before solvation and simulation in GROMACS.
Combining with Other Preprocessing Steps
After targeted water removal, you can perform additional preprocessing from the wizard, such as removing alternate locations, removing unnecessary ligands or ions, and optionally adding hydrogens. These steps integrate seamlessly in the same interface under Home > Prepare.
This integrated process not only saves time but also reduces the risk of preparing a structurally inconsistent system. It’s a small optimization that can have a meaningful impact on both simulation accuracy and efficiency.
To learn more about system preprocessing with the GROMACS Wizard in SAMSON, visit the original documentation page: https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.