One of the constant challenges faced by structural biologists and molecular modelers is trying to compare only a specific region of interest within proteins. Protein structures are big, often composed of hundreds or thousands of residues, but researchers are frequently interested in just a short alpha-helix, a beta-sheet, or a binding pocket that plays a crucial role in function or interaction.
Most molecular visualization tools allow for full-protein superposition, but aligning just a small region — like the N-terminal helix in two hemoglobin variants — often involves custom scripting or manual adjustment. That’s where SAMSON’s Protein Aligner comes in handy with its region-specific alignment feature.
Why Region-specific Alignment Matters
Global protein alignment tends to average out differences across the entire structure, which can mask important local similarities or differences. This is especially problematic in these situations:
- Conformational changes limited to a domain or loop
- Studying conserved motifs across homologous proteins
- Designing drugs targeting a localized protein region
To illustrate, consider aligning two hemoglobins where amino acid sequences globally differ but the N-terminal helices are structurally conserved. Traditional whole-protein alignment won’t highlight this nuance. With SAMSON, you can select just those helices and realign specifically based on them.
Select and Align Only What Matters
Using SAMSON’s Protein Aligner, zoom in on the residues you’re interested in — for instance, select the first 20 residues of each structure in the sequence viewer. These correspond visually to pink alpha-helices in the structure viewport:
Once selected, a small alignment button appears (in the form of an RMSD value such as 0.0 Å). Click that to instruct SAMSON to perform alignment only on the chosen residues. The result is a realignment that highlights very subtle resemblances between these protein segments:
It’s Interactive and Flexible
You can make this process dynamic:
- Hover over residues in the sequences to see detailed information.
- Select multiple non-consecutive residues using Ctrl/Cmd or Shift.
- View changes reflected in real time in SAMSON’s viewport.
This means you’re not locked into static comparison. You can experiment, iterate, and visually confirm which structural parts align optimally. For protein designers or structural bioinformaticians, this reduces friction in hypothesis testing and model inspection.
Want to explore more? Check out the full documentation here: SAMSON Protein Aligner documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.