When preparing molecular systems for simulation, removing water molecules is a common step. However, not all waters are useless. Some are tightly bound or located in active sites and play critical roles in structure and function. Deleting all crystal waters by default might lead to inaccurate simulations or the loss of important interactions.
This is a frequent pain point for researchers using GROMACS or similar platforms. Fortunately, the GROMACS Wizard in SAMSON provides a simple way to selectively remove only the unwanted waters—those located far from the active site—while preserving functional ones.
Why Some Waters Matter
Crystallographic structures often contain water molecules. While many are artifacts of crystallization conditions, some are conserved across multiple structures or form strong interactions within the binding site. These can stabilize ligand interactions, support hydrogen-bonding networks, or contribute to enzymatic function.
Removing all crystal waters might streamline the system, but it can also discard these important waters, potentially degrading the quality of your simulation.
Step-by-Step: Deleting Waters Outside the Active Site
Below is a guide to using the selection tools in SAMSON to keep key waters and remove the rest:
- Select the active site. This can be atoms, residues, or molecular fragments including ligands or tightly bound waters that you want to preserve.
- Right-click on your selection in the Document view or directly in the Viewport, and choose Expand selection > Advanced.
- In the pop-up dialog:
- Set Water as the Node type.
- Choose selection criteria as beyond a certain distance (e.g., 5Å) from your current selection.
Use Auto-update to preview and adjust the threshold as needed.
- Click OK to perform the selection. Review the highlighted waters to confirm they are indeed non-essential.
- Right-click the selection and choose Erase selection. This will remove all waters outside the defined active site.
This method avoids the risks of automatic deletion and gives you full control over which waters remain in your system. It’s especially useful in complex binding studies, enzyme mechanism simulations, or when using X-ray validated structural data.
A Few Tips
- Start with a moderate distance (e.g., 5Å) for the beyond threshold, then adjust based on structure complexity.
- Use visual cues and distance measurements to double-check proximity to key residues.
- Don’t assume water molecules with generic labels like HOH are unimportant—some may still be functionally relevant.
To learn more, visit the original documentation page: SAMSON GROMACS Wizard – Pre-processing of the System.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.