When setting up a molecular simulation, one common obstacle is deciding what to remove from crystal structures—and what to keep. Water molecules, in particular, can be a source of confusion. While loosely bound crystal waters are typically removed before simulation, tightly bound waters—especially those found at active sites—are often critical for protein function and should be retained.
If you’ve ever struggled with identifying and selectively deleting water molecules before running MD simulations with GROMACS, this guide is for you. SAMSON’s GROMACS Wizard makes it easy to do exactly that—without scripting or switching between software.
Why remove water in the first place?
Structures from the Protein Data Bank often contain water molecules that are crystallographic artifacts rather than biologically relevant. These are typically removed before topology generation to avoid unnecessary complexity during simulation. However, some waters participate in hydrogen bonding, stabilize protein conformation, or even take part directly in catalysis. Removing these could lead to unrealistic dynamics or loss of key interactions.
How to selectively remove crystal waters in SAMSON
SAMSON provides a simple workflow for distinguishing functional waters from the rest, allowing you to preserve biologically important ones while cleaning up the system. Here’s how:
- Select key structures: Begin by selecting the active site (such as ligand or key residues) in the Viewport or Document view.
- Expand to nearby waters: Right-click the selection and choose Expand selection > Advanced. In the dialog that opens, set the Node type to Water and choose to select water molecules beyond a certain distance—typically 5 angstroms or more.
- Auto-update to verify: Enable the auto-update checkbox in the selection dialog to preview your selection. This helps you avoid mistakenly selecting waters you want to keep.
- Erase and clean: Once confirmed, right-click and select Erase selection to remove all non-functional waters.
Why this helps
This step is crucial if you’re trying to maintain the biological integrity of your system. It also circumvents potential issues with force-field parameterization, since water models need to be consistent throughout your simulation. Removing well-chosen sets of water molecules reduces computational overhead while still preserving relevant interactions.
Things to watch out for
- Don’t remove waters that are hydrogen-bonded to the ligand or the protein’s catalytic residues unless you’re certain they aren’t essential.
- If you plan to manually add your own water box later in GROMACS, ensure you don’t remove tightly bound waters needed during topology generation.
This refined preparation approach is part of SAMSON’s GROMACS Wizard and helps streamline the pre-processing stage for MD simulations. Whether you’re new to molecular modeling or experienced, this feature can help you make more informed choices while preparing simulation-ready systems.
To learn more about pre-processing systems with GROMACS Wizard in SAMSON, visit the full documentation at https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/.
SAMSON and all SAMSON Extensions are free for non-commercial use.
Get SAMSON at https://www.samson-connect.net.