How to Compare Protein Sequences and Structures Side by Side in SAMSON

When comparing proteins across species or mutations, understanding the conserved and variable regions can be critical for tasks like predicting functional sites, studying evolution, or preparing templates for homology modeling. However, managing both sequence and structural alignments can be unwieldy, especially if switching between multiple tools.

With SAMSON’s Protein Aligner, you can align and interact with protein sequences and structures all in one place. In this post, we’ll walk through how to perform a sequence alignment using two example proteins, and how to analyze the aligned results directly in the SAMSON interface.

Step 1: Load Example Proteins

We’ll align hemoglobins from different species using their PDB codes 1DLW and 1RTX:

Go to Home > Fetch.
Enter 1DLW 1RTX in the input field.
Click Load.

Fetch PDBs

Tip: You can use Home > Prepare to clean up the system by removing waters, ligands, etc.

Step 2: Launch the Protein Aligner

After loading the structures, open the aligner via Home > Align:

Protein Aligner Interface

Step 3: Align Sequences

You can align sequences in two modes:

Align sequences (by structure): aligns whole models.
Align sequences (by chain): aligns each chain separately—useful for oligomers.

Click either alignment button to generate the sequence alignment.

Align sequences

Step 4: Highlight Conserved Features

To compare residue properties (such as charge or similarity), activate the Highlight residues option:

Highlight residues

This helps visually identify conserved regions that may be functionally relevant.

Step 5: Interact with the Sequences

You can explore sequences more deeply with the interactive capabilities of the aligner:

Hover to view residue info and highlight them in the viewport.
Click to select a residue and its aligned partners.
Use Shift, Ctrl/Cmd, or Alt for multi-selection or exclusion.

Select residues from sequences

Use Case: Investigate Conserved Alpha Helices

Suppose you’re interested in the N-terminal alpha-helices of both hemoglobins:

Select the first 20 residues in each sequence.

Selecting residues for alignment

Click the alignment button next to the selection (e.g., the RMSD score) to align only those parts:

Alignment based on selected residues

This type of region-specific alignment is useful when global superposition fails to highlight functionally relevant similarities.

To learn more, visit the SAMSON documentation at: https://documentation.samson-connect.net/tutorials/protein-aligner/protein-aligner/

SAMSON and all SAMSON Extensions are now free for non-commercial use. This makes it easier than ever for academic researchers, educators, and students to explore molecular design and modeling without barriers.