One of the subtle but essential tasks in preparing a molecular system for a GROMACS simulation is deciding which water molecules to keep. While removing all crystal water molecules might simplify pre-processing, it may also mean losing functionally relevant water near the active site. Unfortunately, automated preprocessing tools often provide only all-or-nothing deletion choices. Thankfully, SAMSON’s GROMACS Wizard offers a practical solution to this nuance, helping you retain only the waters that matter. 🧪💧
During crystal structure import, many structures from the Protein Data Bank contain bound water molecules that are either disordered, loosely bound, or play no functional role in the biomolecular system you’re interested in simulating. Conversely, some waters in the vicinity of an active site may be tightly bound and structurally important for maintaining the native conformation or reactivity of the system.
Targeted Deletion of Water Molecules
The GROMACS Wizard in SAMSON allows users to delete only water molecules that fall outside a specified distance from a region of interest, such as the active site. Here’s how you can use it effectively:
- Select the key structures in or near the active site: this might include the ligand, nearby residues, and any tightly bound waters you wish to preserve.
- In the Document view or Viewport, right-click your selection and go to Expand selection > Advanced.
- In the dialog that appears, choose Water as the node type. Then, define a distance (e.g., 5 Å) and choose beyond as the selection criterion.
- You can use the Auto-update option to see in real-time which waters would be selected based on your input.
- Click OK, verify the selection, and then right-click to choose Erase selection.
This approach keeps tightly bound water near the active site while discarding unessential molecules that might interfere with solvation or electrostatics setup during later simulation steps.
Why This Matters
Most force fields do not require the presence of crystal waters unless they play a specific role. Deleting all of them removes unnecessary atoms and can speed up equilibration, but doing so indiscriminately can sometimes wreck biologically relevant interactions. Manual selection or scripting in command-line tools (e.g., pdb2gmx and editconf in GROMACS CLI) usually requires significant care and time.
SAMSON allows you to visualize, select, and delete relevant portions of your system interactively, simplifying this step without losing control. The balance between automation and customization makes this approach appealing, especially for newcomers.
To learn more about this and additional GROMACS Wizard capabilities in SAMSON, visit the original documentation page here: https://documentation.samson-connect.net/tutorials/gromacs-wizard/preprocess/.
Please note that SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.