Quickly Superimpose Protein Structures with Region-Specific Alignment in SAMSON

When comparing protein structures, modelers often want more than global alignment — sometimes, they need to superimpose specific functional regions or binding domains. This is especially true when exploring conformational variability, studying conserved motifs, or building hybrid models. Yet, many molecular modeling tools offer only whole-structure alignment, which isn’t always sufficient.

SAMSON‘s Protein Aligner extension provides a flexible solution that allows not only whole-structure alignment but also region-specific superposition. Here’s how it works and why it can help streamline your structural analysis workflows.

Why Structural Alignment by Region?

Let’s say you are comparing homologous proteins from different organisms. You notice that their active sites — though buried in different environments — are structurally conserved. Rather than aligning entire structures (which could have diverged elsewhere), it makes more sense to focus on just those catalytic regions to highlight shared functional motifs.

Region-specific alignment makes this possible, by allowing you to select particular residues and align only those — preserving relevant local geometry while ignoring unrelated global differences.

How to Perform Region-Specific Alignment in SAMSON

Once you’ve fetched or loaded your structures and opened the Protein Aligner from Home > Align, follow these steps:

  1. Visually inspect the structures and sequences of both proteins.
  2. In the Protein Aligner interface, highlight the region of interest by selecting the corresponding residues (e.g., the first 20 residues) in both sequences.
  3. Click the alignment button located next to the selected residues (denoted by the RMSD value or a 0.0 Å label).

This operation will superimpose the proteins based only on the selected residues. The rest of the structures will remain in their original relative positions, allowing for a focused comparison of the chosen region.

Selecting residues for alignment

Alignment based on selected residues

When to Use this Approach

Region-specific alignment is useful in many scenarios:

  • Analyzing point mutations – focus on segments with known variations to understand local structural effects.
  • Comparing ligand-binding sites – align pockets or fragments to assist in virtual screening prep.
  • Modeling insertion-deletion regions – see how structural loops evolve around conserved cores.
  • Educational demonstrations – highlight particular helices, sheets, or motifs for teaching purposes.

Visual Cues Matter

To improve clarity, you can use the Ribbons view from Visualization > Visual model > Ribbons to better see secondary structures. Coloring each protein differently helps emphasize their similarities and differences post-alignment.

Combine this with tooltip-based inspection or clickable residue information to get the full picture of your alignment decisions.

More Than Just Alignment

The Protein Aligner isn’t just an alignment utility — it enables actionable insights downstream. For example, you can:

  • Export the alignment for homology modeling or comparative docking.
  • Map conserved residues onto functional domains.
  • Iteratively align different domains or structural units to explore flexibility.

If you often work with homologous structures or domain-based comparisons, this feature can genuinely save you time and reduce the potential for misaligned interpretations.

To learn more about using the Protein Aligner in SAMSON, visit the original guide at SAMSON’s 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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