Align Specific Protein Regions to Compare Local Conformations in SAMSON

Comparing protein structures often requires more than just global alignment. In many molecular modeling projects, only a specific domain or region—such as an active site, a loop, or a conserved helix—is of interest. Aligning full proteins may obscure meaningful local similarities or differences. Fortunately, SAMSON’s Protein Aligner extension offers the ability to align proteins based on selected residues only, making it easier to focus on what truly matters for your research 🔍.

Why Align Only a Region?

Global superposition may dilute structural similarity in highly conserved regions by averaging out larger conformational differences elsewhere in the molecule. Local-scale alignment solves this problem, enabling more precise visualization and measurement of small but functionally significant differences.

For example, you may want to:

  • Compare alpha-helical conformations across homologs or mutants
  • Align known ligand-binding pockets to guide drug design
  • Evaluate homology models against reference fragments
  • Visualize local structural conservation while ignoring unrelated flexibility

How to Align Selected Regions in SAMSON

Here’s a quick guide to using region-specific alignment in SAMSON:

  1. Load your proteins. For instance, open the Fetch dialog via Home > Fetch and input the structure codes 1DLW and 1RTX to load two hemoglobin variants.
  2. Open Protein Aligner via Home > Align.
  3. Use the sequence viewer to select the parts of interest in both proteins. To do this, click and drag across the first 20 residues in each sequence for this specific example of N-terminal helices.
  4. Click the alignment button next to the selection — this shows the alignment RMSD (distance) and performs the superposition only on the selected regions.

Selecting residues for alignment

Alignment based on selected residues

Visualizing the Result

After alignment, you’ll see only the selected fragments aligned in 3D. This makes it easier to:

  • Directly compare backbone traces or secondary structures
  • Measure local deviations using RMSD
  • Spot insertions or substitutions that affect geometry

If you’d like to change the visualization to better distinguish the aligned regions, you can enable Ribbons via Visualization > Visual model > Ribbons, and create separate models per protein to color them differently.

When Should You Use It?

Region-specific alignment is especially useful during:

  • Homology modeling — to validate the structural similarity of a modeled fragment
  • Drug binding site comparison — to align pockets between species for selectivity studies
  • Mutation impact analysis — to isolate structural effects from global shifts

This approach gives you the flexibility to focus your analysis and optimize your alignment workflow based on real biological questions, rather than being limited to full-molecule superposition.

To learn more, check out the Protein Aligner documentation in SAMSON.

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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