How to Align Specific Regions of Proteins in SAMSON

When comparing proteins, researchers often face the challenge of aligning only a specific region of interest — for instance, a conserved binding pocket or a particular structural motif — rather than the entire protein. This type of region-specific alignment can provide deeper insight into evolutionary conservation, functional mechanisms, or even guide structure-based drug design.

The Protein Aligner tool in SAMSON offers a streamlined way to perform this task with both sequence and structural precision. In this post, we’ll walk through how to use SAMSON to carry out a region-specific protein structure alignment using an example involving two hemoglobins: 1DLW and 1RTX.

What Problem Does This Solve?

Whole-protein alignment doesn’t always yield meaningful comparisons, especially when structural variations outside of your region of interest may skew the results. By focusing alignment on a specific segment – say, 20 residues at a functional site – you can obtain more accurate insights with lower root mean square deviation (RMSD) and clearer structural correspondence. This is especially useful in:

  • Conserved-site analysis across species
  • Comparing mutated versus wild-type structures
  • Refining models for fragment-based drug design

Example: Aligning the First 20 Residues

Start by fetching the two proteins from the Protein Data Bank using SAMSON’s Home > Fetch feature. Use the PDB codes:

  • 1DLW – Hemoglobin from one species
  • 1RTX – Hemoglobin from another species

Fetch PDBs

After import, launch the Protein Aligner using Home > Align, and both models will be loaded into the alignment interface automatically. Now, to compare specific regions:

  1. Scroll to the beginning of both protein sequences.
  2. Select the first 20 residues from each sequence using click + Shift.
  3. Click the small align button that appears next to the selected residues. This will align the structures based only on those residues.

Selecting residues for alignment

Alignment based on selected residues

Check the resulting structural alignment in the viewport. You should notice a tighter overlap in the selected region compared to the global structure. This allows for a more accurate RMSD reporting for just that segment, and a clear view of structural correspondence.

Visual Tips

To better visualize the result, enable ribbons via Visualization > Visual model > Ribbons and assign different colors to each structure. This makes it easy to distinguish the aligned regions:

  • Select one molecule, then apply a visual model
  • Do the same for the second molecule with a different color

Why It Matters

Whether you’re analyzing conserved regions, evaluating binding site flexibility, or comparing mutations, SAMSON’s region-specific alignment gives you the control to focus on what’s biologically important — without getting lost in structural noise elsewhere in the protein.

To learn more, visit the full Protein Aligner documentation page.

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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