Improving Protein Superposition with Region-Specific Alignment in SAMSON

When comparing protein structures, overall alignment using root-mean-square deviation (RMSD) is often the first go-to method. But what if you’re only interested in a particular region of a protein? Maybe the active site, a conserved domain, or an alpha-helix that’s structurally conserved across species. Aligning full proteins can sometimes hide the finer, regional similarities that matter most to your work.

This is where region-specific alignment becomes an essential tool — and SAMSON’s Protein Aligner extension makes it easy to do just that.

Why focus on regions instead of full structures?

Protein structures often consist of multiple domains or flexible parts. Structural differences in less relevant regions can increase global RMSD and obscure conserved areas that are biologically meaningful, like binding sites or conserved motifs. Focusing your alignment on relevant regions can improve the interpretability of your models for ligand docking, mutation effect predictions, or homology modeling.

How to perform region-specific alignment in SAMSON

Let’s say you’re looking at two hemoglobins with similar alpha-helices at the N-terminal end. To align just these helices using the Protein Aligner in SAMSON, follow these steps:

  1. Load your structures (for example: 1DLW and 1RTX) using Home > Fetch.
  2. Launch the Protein Aligner via Home > Align.
  3. Select the specific residues you want to align in both sequences. Hold Shift to select consecutive residues — for example, the first 20 residues in each protein.
  4. Click the alignment button (e.g., the one showing 0.0 Å) next to your selection to align only those parts.

Selecting residues for alignment

After alignment, you’ll see the selected regions superimposed based on their local structural similarity:

Alignment based on selected residues

Use cases for region-specific alignment

  • Compare active sites in enzyme homologs to infer conserved mechanisms.
  • Measure local structural effects caused by point mutations.
  • Focus alignment on ligand-binding pockets for structure-based drug design.
  • Assist in homology modeling when only part of the structure is available.

A practical advantage

Because the Protein Aligner in SAMSON allows you to interactively select and align specific residues, it removes the need for scripting or switching between multiple tools. The color-coded sequence alignment and instant 3D feedback make it easy to focus your modeling efforts where it truly matters.

This region-specific alignment functionality allows for more precise structural comparisons, particularly in workflows such as lead optimization, structure-function analysis, and academic study of protein evolution. It’s a simple feature that can yield more relevant models for your particular questions.

To see the full guide, including videos and additional tips for using the Protein Aligner, visit the original documentation page at this link.

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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