Tired of Misaligned Models? Here’s How to Align Proteins by Region in SAMSON

When comparing protein structures, it’s common to find that overall alignment doesn’t always capture biologically relevant differences—or similarities. Sometimes you’re only interested in a specific region, like the active site or an alpha-helix that’s been mutated. Trying to force a global superposition isn’t just inefficient—it can obscure the biological insights you’re after.

That’s where region-specific alignment comes in. With SAMSON’s Protein Aligner Extension, you can focus directly on the part of the protein that matters most to your workflow.

Why Region-Specific Alignment Matters

  • You want to study conserved motifs or binding pockets without interference from flexible termini.
  • You suspect that local changes impact function, even if the global fold seems preserved.
  • You’re building models from homologs and want more accurate template-target matching in functional areas.

Step-by-Step: Align Selected Residues Only

Let’s look at how to isolate and align specific regions using SAMSON. Suppose we want to align only the first 20 residues of two hemoglobins (1DLW and 1RTX), which appear similar in structure but aren’t properly superimposed after a global alignment.

  1. Fetch proteins via Home > Fetch using the IDs: 1DLW and 1RTX.
  2. Open the Protein Aligner via Home > Align.
  3. In the sequence pane, select the first 20 residues in each sequence. (Hold Shift for range selection.)
  4. Click the alignment button next to the selection (it typically shows 0.0 Å initially).

That’s it—the structures will now be aligned based only on those residues, and the displayed RMSD will reflect the local fit.

Selecting residues for alignment

Alignment based on selected residues

Some Practical Tips

  • Color per chain: Use ribbons from Visualization > Visual model > Ribbons and apply them separately to each chain to better distinguish them.
  • Toggle views: Simplify your visualizations by enabling or disabling atomistic views in the Document view.
  • Select from viewport: You don’t need to rely solely on the sequence view. Clicking a region in the 3D view highlights and selects it in Protein Aligner, too.

When to Use This Approach

This method is practical for:

  • Comparing loop movement between wild type and mutant forms
  • Focusing on enzymatic sites during inhibitor design
  • Verifying homologous regions across species with structural divergence

By targeting regions that matter, you reduce noise in the alignment and focus on biologically relevant shifts or conservation.

Want to Continue?

You can export aligned models, map conserved residues, or apply the same technique to multiple chains. If you’d like to explore all available features, including sequence alignment and visual aids, check out the full guide below.

Learn more in the full documentation.

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

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