Want More Control Over Structural Alignments? Try Region-Specific Protein Superposition

When working with homologous proteins from different organisms or mutant variants, automated structural alignment tools are helpful—but often, they align the entire structure. This can be problematic if you’re interested in comparing specific regions only, like a conserved binding pocket or a flexible loop.

Fortunately, SAMSON’s Protein Aligner makes it simple to perform region-specific alignment based only on the residues that matter to you. Here’s how to take advantage of it when whole-protein alignment isn’t enough.

📌 The Challenge: Partial Structural Similarity

Let’s say you’re looking at two hemoglobins from different organisms (PDB IDs: 1DLW and 1RTX). A whole-protein alignment might highlight overall similarity, but what if you only care about a conserved helix at the N-terminus or a loop that’s important for ligand binding?

When only part of the structure is functionally relevant—or structurally conserved—you need finer control over what gets aligned.

🎯 Region-Specific Superposition in SAMSON

Here’s how to align just a part of your molecules in SAMSON using the Protein Aligner extension:

  1. Load your proteins (e.g. 1DLW and 1RTX) using Home > Fetch.
  2. Prepare the structures if needed via Home > Prepare to remove waters or ligands.
  3. Launch the Protein Aligner from Home > Align.
  4. Select the specific residues you want to use for alignment. For example, you can choose the first 20 residues from each sequence which correspond to the N-terminal helices:

Selecting residues for alignment

  1. Once selected, click the alignment button next to the residue selections (usually shows an RMSD like 0.0 Å).

Region-specific alignment of structures

🔬 Why Region-Based Alignment Is Useful

  • Compare ligand-binding paths across homologs while ignoring unrelated structural domains.
  • Superimpose flexible loops or domains that move independently of the protein scaffold.
  • Investigate residue-level variation in specific structural motifs without distortions from unrelated regions.

This feature is particularly useful in homology modeling and ligand design, where local alignment accuracy can significantly influence downstream predictions.

🔧 Tips for Better Visual Analysis

  • Enable Ribbons via Visualization > Visual model > Ribbons to emphasize secondary structure.
  • Apply different colors to aligned structures to distinguish them easily.
  • Use Highlight residues to compare physicochemical properties like similarity and polarity across aligned regions.

📘 Want to Dive Deeper?

You can explore sequence alignment modes, interaction tools, and export options in the full documentation page: Protein Aligner Documentation.

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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