Protein alignments play a crucial role in structure-based molecular design, helping researchers uncover conserved regions, highlight conformational differences between homologs, and guide homology modeling. But what happens when you’re only interested in a specific part of the protein? That’s a common scenario in molecular modeling—you’re studying a binding pocket, a flexible loop, or perhaps a motif conserved across families. Aligning whole proteins might bury the local information under global structural differences.
If you’ve ever faced this, SAMSON’s Protein Aligner offers a direct and practical way to focus your alignment where it matters most: on the region of interest. This blog post shows how to align specific protein segments—like matching individual helices across related structures—instead of entire chains.
Why You Might Need Local Alignment
Say you’re working on two protein homologs. Their overall folds may differ slightly, but one motif—the first 20 residues, for instance—looks structurally conserved and functionally relevant. Whole-protein superposition may misalign that region if the other domains don’t match.
That’s where local alignment comes in. Instead of aligning the entire structures, you can compare just the relevant regions to reveal subtle but important functional similarities.
Aligning Selected Regions in SAMSON
Let’s take an example from SAMSON’s tutorial, aligning two hemoglobins (1DLW and 1RTX):
- Use Home > Fetch to load both structures by entering
1DLW 1RTX. - Go to Home > Align to open the Protein Aligner.
- Inspect the sequences. Suppose you’re interested in the N-terminal helices; select the first 20 residues in both sequences manually.
- Hover over residues to confirm their identity, or use Shift/Ctrl (or Cmd on macOS) to select multiple residues accurately.
- Once selected, click the alignment button (displays RMSD, such as
0.0 Å) near either sequence. This aligns the structures based solely on those residues.
The result? A structural overlay that focuses on just the residues that matter to you:
Tips for Effective Local Matches
- Zoom in visually: Use Visualization > Visual model > Ribbons to generate separate visual models for each protein.
- Color them differently to immediately distinguish one from the other in the viewport.
- Toggle residue highlights to emphasize conserved or different biochemical properties across aligned regions.
This selective alignment allows precise analysis of functionally critical motifs and can drive better insights in ligand design or mutation studies.
In Summary
Global alignment is a good starting point, but in many modeling workflows, precision lies in the details. Whether you’re comparing helices, loops, or active sites, SAMSON’s region-specific protein alignment lets you tailor the view to your hypothesis. Rather than wrestling with misaligned models, you focus exactly where your science needs it.
To learn more, check out the full documentation page: Protein Aligner Documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.