One common challenge in molecular modeling is selectively optimizing only certain parts of a molecular structure while leaving the rest untouched. This becomes particularly relevant when working on large biomolecules, designing ligands, or when assessing localized conformational changes. Minimizing an entire system each time can be inefficient if your focus is just on one fragment.
Thankfully, SAMSON provides a solution for this through a technique called partial minimization. This functionality allows you to “freeze” parts of your molecule while minimizing only the region you’re interested in, enabling more targeted and efficient optimizations. Here’s how you can do it.
Freeze What You Don’t Want to Move
The concept is simple: frozen atoms stay fixed during minimization. You can freeze either a specific selection or the entire structure, then unfreeze just the portion you’re working on.
For example, if you’re interested in optimizing just one flexible chain of a protein while keeping the rest static, you can:
- Select the entire molecule (or leave the selection empty).
- Click Edit > Freeze to freeze either the selection or, if empty, everything.
- Select the region you would like to minimize (e.g., a flexible loop, side chain, or ligand).
- Click Edit > Unfreeze to make only those atoms movable.
- Click Edit > Minimize to begin the interactive minimization of the selected region.
- Click Edit > Minimize again to stop when satisfied.
- Finally, unfreeze all by selecting the structure (or nothing), then clicking Edit > Unfreeze.
Frozen atoms are indicated in the viewport with a dark blue overlay, making it easier to see which regions are locked.
Why Partial Minimization Can Help You
There are several scenarios where partial minimization can be helpful:
- Ligand docking: After docking, you may want to refine only the ligand’s geometry while keeping the protein fixed.
- Protein loop modeling: You might want to adjust just a flexible loop region based on experimental data.
- Constrained minimization: Preserve crystallographic or known structural arrangements while locally optimizing a new modification.
Thanks to SAMSON’s interactive mode, you can adjust selections and utilize freeze/unfreeze features in real-time. This makes it easier to experiment with molecular refinements and see results quickly without rerunning full system calculations.
Here’s a snapshot of the preferences you might use to control this behavior:
Both interactive and simulator-based minimization options are available, but freezing/unfreezing is particularly effective in interactive workflows.
To see this feature in action, check out this video demonstration from the documentation:
By controlling which atoms move and which remain fixed, partial minimization gives you far more flexibility and control over your modeling process—saving you time while ensuring structural accuracy in the areas that matter most.
To learn more about all minimization options in SAMSON, visit the full documentation page here: https://documentation.samson-connect.net/users/latest/minimizing/.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.