How to Minimize Part of a Molecule in SAMSON Without Affecting the Rest

When working with complex molecular systems, it’s common to want to optimize the geometry of only a specific part of a molecule—without disturbing the rest of the structure. This can be especially useful during refinement workflows, local repairs in crystal structures, or interaction energy studies where only a part of a context molecule is under investigation.

SAMSON, the integrative molecular design platform, provides an intuitive way to perform such selective geometry optimization through freezing and unfreezing atoms. Here’s how you can focus minimization on just the region you’re interested in.

Why Partial Minimization?

Let’s say you have a protein-ligand complex, and you’ve just modified the ligand. You want to optimize it so that its conformation is more realistic, but you don’t want the surrounding protein to move. If you minimize everything, even the protein atoms may shift slightly—potentially complicating comparisons or disrupting a validated environment. That’s where freezing helps.

The Workflow

To minimize only a part of a molecule in SAMSON, you can follow these steps:

  1. Freeze everything: Select the whole molecule, or keep the selection empty to apply changes to the whole document. Then, go to Edit > Freeze. This fixes the positions of all atoms so they’re not affected by minimization.
  2. Select the part you want to optimize: Use the selection tools to choose only those atoms that should be minimized.
  3. Unfreeze this part: Go to Edit > Unfreeze. This releases only the selected atoms for movement during minimization.
  4. Start the minimization: Use Edit > Minimize or the shortcut key Z to begin the interactive energy minimization. You’ll see how the selected part of the molecule relaxes into a more stable shape, while frozen atoms stay put.
  5. Stop when satisfied: Simply click Edit > Minimize again or press Z to stop.
  6. Unfreeze if needed: You can go back to Edit > Unfreeze to release all positions and allow the full structure to be edited again, or keep parts frozen according to your ongoing work.

It’s important to remember that frozen atoms are visually represented in the viewport with a dark blue overlay, making it easier to understand which atoms are fixed and which are allowed to move.

This simple but powerful method lets you operate with surgical precision within molecular models. Whether you’re adjusting torsions in a side chain, optimizing a binding pocket, or relaxing a distorted loop, freezing enables safe, localized optimization.

You can see this in action in the video below, where only a portion of a molecule is minimized while the rest remains unchanged:

To learn more about minimization options in SAMSON, including how to minimize entire molecules or use simulation-based methods, please visit the full documentation page.

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

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