When preparing protein structures for molecular dynamics simulations, one common issue is dealing with water molecules in crystal structures. Should you keep them all? Delete them all? The reality is more nuanced, especially when some water molecules are functionally important – for example, those tightly bound in the active site.
SAMSON’s GROMACS Wizard offers a convenient and visual way to delete just the water molecules you don’t need. This blog post focuses on how to selectively remove crystal waters outside of the active site while keeping essential ones intact.
Why it’s important
Crystal structures often contain water molecules derived from crystallization conditions. While some of these may be functionally essential (e.g., bridging water in active sites), many are simply noise for simulation purposes and may interfere with solvation or parameterization steps.
Blindly deleting all waters risks removing important structural components. Leaving them all in may result in unnecessary computational complexity and force field mismatch errors.
How to do it with SAMSON
Here’s how SAMSON helps you make this selection visually and efficiently:
- Select the active site: Use SAMSON’s selection tools to pick atoms, residues, or molecules defining your protein’s active site. You can click directly in the Viewport or use the Document view.
- Expand to nearby waters: Right-click on your selection and select Expand selection > Advanced. In the dialog, choose Water as the node type, and pick atoms “beyond” a certain distance (e.g., 5Å). Auto-update helps you visualize the selection in real time.
- Review the selection: Check whether the highlighted water molecules make sense — they should lie outside of the active pocket. This reduces your chances of removing coordinated or functionally relevant waters.
- Delete selection: Once satisfied, right-click and choose Erase selection. Done.
This workflow is especially useful when working with systems where manual handpicking of waters would be infeasible. Quick visual feedback reduces human error and ensures you preserve only what contributes to the biochemistry you’re studying.
Visual example
With this approach, you stay in control of your simulation setup while maintaining reproducibility and clarity for downstream analysis. It also helps avoid errors during topology generation, particularly for simulations involving force fields that require exact atomic configurations.
If you’re still undecided about what waters to keep, look at their B-factors, hydrogen bonding patterns, or literature references for your system.
To learn more, visit the full documentation: Pre-processing with GROMACS Wizard.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at www.samson-connect.net.