Protein Mutation Analysis

Protein Mutation Analysis

Analyze the functional impact of protein mutations using MutaPLM and visualize protein structures.

When to Use

• User provides a UniProt ID and mutation (e.g., "P04637 R248Q")
• User wants to understand the effect of a specific mutation
• User needs to visualize a mutated protein structure
• Research on disease-associated genetic variants

Workflow

Step 1: Retrieve Protein from UniProt

from open_biomed.tools.tool_registry import TOOLS

tool = TOOLS["protein_uniprot_request"]
result, message = tool.run(accession="P04637")
protein = result.get("protein")

Step 2: Explain Mutation with MutaPLM

mutation_tool = TOOLS["mutation_explanation"]
mutation_result, _ = mutation_tool.run(
    protein=protein,
    mutation="R248Q"  # Format: OriginalAA + Position + MutantAA
)

Step 3: Predict Structure with ESMFold

folding_tool = TOOLS["protein_folding"]
fold_result, _ = folding_tool.run(protein=protein)
predicted_protein = fold_result.get("protein")

Step 4: Visualize Protein Structure

viz_tool = TOOLS["visualize_protein"]
viz_result, _ = viz_tool.run(protein=predicted_protein, style="cartoon")

See examples/basic_analysis.py for the complete implementation.

Expected Outputs

Mutation Format

Single amino acid mutation: OriginalAA + Position + MutantAA

Error Handling

Missing Model Checkpoints

Symptom: FileNotFoundError or AttributeError

Solution: Check checkpoints exist:

• ./checkpoints/server/mutaplm.pth
• ./checkpoints/esm2/650m/
• ./checkpoints/biomedgpt-lm/

Fallback: Use web search for mutation literature.

Position Out of Range

position = int(mutation[1:-1])
if position > len(protein.sequence):
    print(f"Error: Position exceeds sequence length")

See references/troubleshooting.md for detailed error handling.

Interpretation

MutaPLM Output

• Disease association: "In [cancer type]..." indicates known disease link
• Functional change: Describes altered protein function
• Structural impact: May mention stability effects

ESMFold Confidence

Example

Input: P04637 R248Q

Step 1: Retrieved TP53 (393 aa)
Step 2: "In lung cancer, mutation R248Q..."
Step 3: Structure predicted (~8s)
Step 4: Visualization saved

Output: Mutation analysis + structure + visualization

Prerequisites

Model checkpoints required (see references/troubleshooting.md):

• MutaPLM, ESM2, BioMedGPT-LM, ESMFold

Related Tools

• protein_pdb_request - Get existing PDB structures
• protein_question_answering - Ask about protein function
• export_protein - Save structure to PDB format