Need to Minimize Just a Part of a Molecule? Here’s How.

When modeling molecules, especially large or complex systems, it’s common to need to optimize only a part of a molecule while keeping the rest fixed. For example, you might want to relax a portion of a ligand while preserving the geometry of the surrounding protein or scaffold structure. Efficient partial geometry optimization can save time, provide more focused results, and avoid unintended alterations to the entire system. Luckily, SAMSON makes this process straightforward with its interactive minimization tools.

In SAMSON, you can selectively minimize parts of your molecule by freezing the atoms you want to keep fixed and optimizing only those you want to move. This is particularly useful when working on substituted fragments, repairing distorted geometries, or refining docking poses. Here’s a quick guide that walks you through this practical process.

Step-by-step: Minimizing Part of a Molecule

  1. Select and freeze: Start by selecting the atoms you want to keep fixed—this is usually the scaffold or backbone. You can also leave the selection empty to freeze everything. Then, go to Edit > Freeze. This will freeze all selected atoms (or the whole system if nothing is selected).
  2. Select what to minimize: Now, choose the specific portion of the molecule you’d like to relax. Maybe it’s a flexible loop, a side chain, or a small ligand fragment.
  3. Unfreeze your selection: Use Edit > Unfreeze to unfreeze the atoms you’ve just selected. These will now be the only parts that are free to move during the minimization.
  4. Activate minimization: Go to Edit > Minimize (or simply press Z) to begin the interactive energy minimization using the embedded Universal Force Field (UFF). You’ll see atoms adjusting their positions to reach a lower energy conformation.
  5. Stop minimization: Press Edit > Minimize again to stop the process when you’ve reached a satisfactory geometry.
  6. Unfreeze all (optional): If needed, restore mobility to your entire system using Edit > Unfreeze with either the system selected or with no selection at all.

Tip: Frozen atoms appear with a dark blue overlay in SAMSON’s viewport, making it easy to visually distinguish between fixed and mobile parts.

Visual Example

Want to see it in action? The screenshot below shows the preferences panel where you can tweak minimization settings:

Interactive minimization preferences

And here’s a quick video that demonstrates minimization with frozen atoms and shows how localized the optimization can be:

This method gives you full control over which parts of your molecule are optimized, helping you focus on what really matters while preserving the rest of your system.

To learn more, visit the full documentation at https://documentation.samson-connect.net/users/latest/minimizing/.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.

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