protein-mutation-analysis

name	protein-mutation-analysis
description	Analyze protein mutations by retrieving protein data, explaining mutation effects, predicting protein structure, and visualizing results. Use this skill when the user asks about protein mutations, wants to understand mutation effects, or needs to analyze genetic variants. Triggers on phrases like "analyze mutation", "explain mutation", "what does this mutation do", "protein variant 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

Step	Output	Description
Retrieve Protein	Protein object	Name, sequence from UniProt
Explain Mutation	Text	Functional impact from MutaPLM
Predict Structure	Protein with 3D coords	Structure from ESMFold
Visualize	PNG file	Rendered protein structure

Mutation Format

Single amino acid mutation: OriginalAA + Position + MutantAA

Valid	Invalid	Reason
R248Q	R248	Missing mutant AA
V600E	248Q	Missing original AA
L858R	ARG248GLN	Use single-letter codes

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

pLDDT Score	Confidence
> 90	High
70-90	Moderate
< 70	Low (disordered)

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