mdhewei/bioinfor-claw/protein-structure-alignment

Protein Structure Alignment

Compare two protein structures by superimposing them via Cα atoms (Biopython Superimposer). Computes global RMSD, highlights divergent regions, and produces a dual-colour interactive 3D viewer.

Trigger examples

• "Align the apo and holo structures of adenylate kinase"
• "Compare 1AKE and 4AKE, what is the RMSD?"
• "Superimpose the AlphaFold model for P00940 against the crystal structure 1TIM"
• "How similar are the WT and mutant protein structures?"
• "Find flexible regions between two conformations of the same protein"

Non-triggers (use a different skill)

• "Show me the structure of a single protein" → use protein-structure-visualizer
• "What domains does my protein have?" → use protein-structure-for-gene
• "Align protein sequences" → use standard sequence alignment tools

Command template

cd protein-structure-analysis/protein-structure-alignment
pip install biopython matplotlib numpy pandas py3Dmol requests
 
# Two PDB IDs
python scripts/protein_structure_alignment.py \
  --pdb1 <PDB_ID_1> \
  --pdb2 <PDB_ID_2> \
  --outdir results/
 
# AlphaFold predicted vs experimental
python scripts/protein_structure_alignment.py \
  --pdb1 <PDB_ID> \
  --uniprot2 <UNIPROT_ACC> \
  --outdir results/
 
# Local files
python scripts/protein_structure_alignment.py \
  --file1 wt.pdb \
  --file2 mutant.pdb \
  --outdir results/
 
# Restrict to one chain and a residue range
python scripts/protein_structure_alignment.py \
  --pdb1 1AKE --pdb2 4AKE \
  --chain1 A --chain2 A \
  --res-start 1 --res-end 180 \
  --outdir results/

All CLI arguments

Parameter decision guide

Outputs

• <PREFIX>.alignment_summary.tsv — global RMSD, n Cα pairs, divergent residue counts
• <PREFIX>.per_residue_rmsd.tsv — per-residue Cα distance after superimposition
• <PREFIX>.per_residue_rmsd.png/.pdf — bar plot coloured green (<1Å) / orange (1–3Å) / red (>3Å)
• <PREFIX>.superimposed.html — interactive 3D viewer: structure 1 in blue, structure 2 in red; divergent residues (>3Å) highlighted in orange sticks
• <PREFIX>.superimposed.pdb — coordinates of structure 2 in the superimposed frame

How it works

1. Fetches both structures from RCSB PDB or AlphaFold EBI (or reads local files)
2. Extracts Cα atoms from both; pairs residues by (chain, resseq)
3. Superimposes structure 2 onto structure 1 using Biopython's Superimposer (SVD-based rigid-body alignment)
4. Computes global RMSD and per-residue Cα distance
5. Writes all atoms of structure 2 in the new (rotated/translated) frame
6. Visualises both structures in py3Dmol with divergent regions highlighted

Failure conditions

• "No common Cα pairs found" → chains or residue numbering don't overlap; specify --chain1/--chain2 or --res-start/--res-end
• Very high RMSD on short alignments → try aligning a specific domain with --res-start/--res-end
• AlphaFold fetch fails → UniProt accession not found; verify at https://alphafold.ebi.ac.uk