Quickly Align Protein Structures Based on Specific Residue Regions

When exploring protein function or designing ligands, it’s often essential to compare specific functional regions, rather than entire protein structures. This is especially true in structure-based drug discovery, homology modeling, and evolutionary studies, where conserved motifs might be hidden among otherwise dissimilar domains.

With SAMSON’s Protein Aligner, you can align entire proteins—or target specific regions for precise structural superposition. If you’ve ever found yourself frustrated by whole-protein alignments that hide local similarities, this tool can help you focus alignment on exactly the region that matters.

Why align only part of a protein?

Full-protein alignment is useful, but sometimes it doesn’t tell the whole story:

  • Active sites or binding pockets may be small, conserved subsequences.
  • Insertions, conformational flexibility, or domain swaps can skew global alignment.
  • Focusing on a specific motif or structural element (like an alpha helix or loop region) can clarify biological insights.

How to align selected regions of proteins in SAMSON

Here’s how to do region-specific structural alignment in SAMSON using the Protein Aligner extension:

  1. Load your proteins. In the example from the documentation, hemoglobins 1DLW and 1RTX are fetched via Home > Fetch.
  2. Launch the Protein Aligner via Home > Align .
  3. In the Protein Aligner interface, locate the sequence panels for both proteins.
  4. Select the region of interest in both sequences. For instance, select the first 20 residues if you’re interested in N-terminal helices that look similar but aren’t superimposed by global alignment.
  5. Click the alignment button next to the selected region (e.g., the one reporting 0.0 Å). This will align the structures based only on these selected residues.

Selecting residues for alignment

Alignment based on selected residues

Tips for working with partial alignments

  • Choose structurally conserved regions for selection to improve RMSD outcomes.
  • Use visualization tools like ribbons for better clarity. You can toggle ribbon models via Visualization > Visual model > Ribbons.
  • Build separate visual models per protein to assign different colors and distinguish alignment effects.

When is region-specific alignment most helpful?

Partial alignment is especially useful when:

  • Comparing homologous domains in multi-domain proteins.
  • Analyzing mutations that only affect specific loops or helices.
  • Superimposing receptor binding regions to study selectivity across species.

Precision matters in molecular modeling. A small shift in one alpha helix can change binding predictions, so being able to target your alignment increases accuracy and insight.

To learn more about aligning proteins in SAMSON—including sequence alignment, full structure alignment, and exporting alignments—visit the official Protein Aligner documentation.

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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