Focusing on Function: How to Align Specific Protein Regions for Better Structural Insight

When comparing protein structures, most tools default to full-chain alignment. But what if you’re only interested in specific regions, like active sites, functional motifs, or conserved helices? Aligning entire proteins can dilute meaningful structural comparisons in such cases.

This is a common pain point for molecular modelers: superimposing proteins based on the entire structure when only part is relevant. Fortunately, SAMSON’s Protein Aligner offers an intuitive way to perform region-specific alignment, letting you focus directly on what matters.

Why You Might Need Region-Specific Alignment

Let’s say you’re studying two homologs and only a small portion—say, the N-terminal helices—is of functional interest. If you use conventional full-length superposition, the alignment might appear poor overall, disguising local similarities. By narrowing the alignment to that one structural region, you get a clearer view of how conserved (or divergent) those residues are in space.

Step-by-Step: Aligning a Specific Region

Here’s how to perform a region-specific alignment using SAMSON’s Protein Aligner extension:

  1. First, fetch the two proteins you’d like to compare. For example, you could fetch hemoglobin structures 1DLW and 1RTX using Home > Fetch.
  2. Then, launch the Protein Aligner via Home > Align.
  3. Click on the sequences shown in the Protein Aligner interface to select the region of interest. In the case below, the first 20 residues in both sequences are selected to focus on N-terminal alpha helices.

Selecting residues for alignment

Once selected, a new button appears in the table beside those sequences. Click it (it may show as “0.0 Å” if there is currently no calculated RMSD) to perform the region-specific alignment.

Alignment based on selected residues

SAMSON will superimpose the structures using only these residues, producing a more accurate comparison in the region you care about most.

Visualization Tips

  • To better see the aligned region, turn on Ribbons in Visualization > Visual model.
  • Create separate ribbon models per protein to apply different colors. It helps distinguish the structures more clearly.

When to Use This Feature

  • Comparing catalytic domains in enzymes
  • Analyzing loop conformations in GPCRs
  • Spotting structural conservation in mutation studies
  • Fitting parts of a large protein into cryo-EM densities

By giving you control over which residues drive the alignment, SAMSON opens the door to more nuanced structural interpretations. It eliminates noise from irrelevant regions and lets you zero in on the features that matter.

This makes region-specific superposition not just more precise, but more interpretable.

To learn more, visit the full documentation at https://documentation.samson-connect.net/tutorials/protein-aligner/protein-aligner/.

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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