protein-structure-retrieval

name	protein-structure-retrieval
description	ToolUniverse workflow — Protein Structure Retrieval
source	https://github.com/mims-harvard/ToolUniverse/tree/main/skills/tooluniverse-protein-structure-retrieval
metadata	null

---

name: tooluniverse-protein-structure-retrieval description: Retrieves protein structure data from RCSB PDB, PDBe, and AlphaFold with protein disambiguation, quality assessment, and comprehensive structural profiles. Creates detailed structure reports with experimental metadata, ligand information, and download links. Use when users need protein structures, 3D models, crystallography data, or mention PDB IDs (4-character codes like 1ABC) or UniProt accessions.

Protein Structure Data Retrieval

Retrieve protein structures with proper disambiguation, quality assessment, and comprehensive metadata.

IMPORTANT: Always use English terms in tool calls (protein names, organism names), even if the user writes in another language. Only try original-language terms as a fallback if English returns no results. Respond in the user's language.

Workflow Overview

Phase 0: Clarify (if needed)
    ↓
Phase 1: Disambiguate Protein Identity
    ↓
Phase 2: Retrieve Structures (Internal)
    ↓
Phase 3: Report Structure Profile

---

Phase 0: Clarification (When Needed)

Ask the user ONLY if:

• Protein name matches multiple genes/families (e.g., "kinase" → which kinase?)
• Organism not specified for conserved proteins
• Intent unclear: need experimental structure vs AlphaFold prediction?

Skip clarification for:

• Specific PDB IDs (4-character codes)
• UniProt accessions
• Unambiguous protein names with organism

---

Phase 1: Protein Disambiguation

1.1 Resolve Protein Identity

from tooluniverse import ToolUniverse
tu = ToolUniverse()
tu.load_tools()

# Strategy depends on input type
if user_provided_pdb_id:
    # Direct structure retrieval
    pdb_id = user_provided_pdb_id.upper()
    
elif user_provided_uniprot:
    # Get UniProt info, then search structures
    uniprot_id = user_provided_uniprot
    # Can also get AlphaFold structure
    af_structure = tu.tools.alphafold_get_structure_by_uniprot(
        uniprot_id=uniprot_id
    )
    
elif user_provided_protein_name:
    # Search by name
    result = tu.tools.search_structures_by_protein_name(
        protein_name=protein_name
    )

1.2 Identity Resolution Checklist

• Protein name/gene identified
• Organism confirmed
• UniProt accession (if available)
• Isoform/variant specified (if relevant)

1.3 Handle Naming Collisions

Common ambiguous terms:

Term	Ambiguity	Resolution
"kinase"	Hundreds of kinases	Ask which kinase (EGFR, CDK2, etc.)
"receptor"	Many receptor types	Specify receptor family
"protease"	Multiple families	Ask serine/cysteine/metallo/etc.
"hemoglobin"	Clear	Proceed (α/β chain specified if needed)
"insulin"	Clear	Proceed

---

Phase 2: Data Retrieval (Internal)

Retrieve all data silently. Do NOT narrate the search process.

2.1 Search Structures

# Search by protein name
result = tu.tools.search_structures_by_protein_name(
    protein_name=protein_name
)

# Filter results by quality
high_res = [
    entry for entry in result["data"]
    if entry.get("resolution") and entry["resolution"] < 2.5
]

2.2 Get Structure Details

For each relevant structure:

pdb_id = "4INS"

# Basic metadata
metadata = tu.tools.get_protein_metadata_by_pdb_id(pdb_id=pdb_id)

# Experimental details
exp_details = tu.tools.get_protein_experimental_details_by_pdb_id(
    pdb_id=pdb_id
)

# Resolution (if X-ray)
resolution = tu.tools.get_protein_resolution_by_pdb_id(pdb_id=pdb_id)

# Bound ligands
ligands = tu.tools.get_protein_ligands_by_pdb_id(pdb_id=pdb_id)

# Similar structures
similar = tu.tools.get_similar_structures_by_pdb_id(
    pdb_id=pdb_id,
    cutoff=2.0
)

2.3 PDBe Additional Data

# Entry summary
summary = tu.tools.pdbe_get_entry_summary(pdb_id=pdb_id)

# Molecular entities
molecules = tu.tools.pdbe_get_molecules(pdb_id=pdb_id)

# Binding sites
binding_sites = tu.tools.pdbe_get_binding_sites(pdb_id=pdb_id)

2.4 AlphaFold Predictions

# When no experimental structure exists, or for comparison
if uniprot_id:
    af_structure = tu.tools.alphafold_get_structure_by_uniprot(
        uniprot_id=uniprot_id
    )

Fallback Chains

Primary	Fallback	Notes
RCSB search	PDBe search	Regional availability
get_protein_metadata	pdbe_get_entry_summary	Alternative source
Experimental structure	AlphaFold prediction	No experimental structure
get_protein_ligands	pdbe_get_binding_sites	Ligand info unavailable

---

Phase 3: Report Structure Profile

Output Structure

Present as a Structure Profile Report. Hide search process.

# Protein Structure Profile: [Protein Name]

**Search Summary**
- Query: [protein name/PDB ID]
- Organism: [species]
- Structures Found: [N] experimental, [M] AlphaFold

---

## Best Available Structure

### [PDB ID]: [Title]

| Attribute | Value |
|-----------|-------|
| **PDB ID** | [pdb_id] |
| **UniProt** | [uniprot_id] |
| **Organism** | [species] |
| **Method** | X-ray / Cryo-EM / NMR |
| **Resolution** | [X.XX] Å |
| **Release Date** | [date] |

**Quality Assessment**: ●●● High / ●●○ Medium / ●○○ Low

### Experimental Details
| Parameter | Value |
|-----------|-------|
| **Method** | [X-ray crystallography] |
| **Resolution** | [1.9 Å] |
| **R-factor** | [0.18] |
| **R-free** | [0.21] |
| **Space Group** | [P 21 21 21] |

### Structure Composition
| Component | Count | Details |
|-----------|-------|---------|
| **Chains** | [N] | [A (enzyme), B (inhibitor)] |
| **Residues** | [N] | [coverage %] |
| **Ligands** | [N] | [list ligand names] |
| **Waters** | [N] | |
| **Metals** | [N] | [Zn, Mg, etc.] |

### Bound Ligands
| Ligand ID | Name | Type | Binding Site |
|-----------|------|------|--------------|
| [ATP] | Adenosine triphosphate | Substrate | Active site |
| [MG] | Magnesium ion | Cofactor | Catalytic |

### Binding Site Details
For drug discovery applications:

**Site 1: Active Site**
- Location: Chain A, residues 45-89
- Key residues: Asp45, Glu67, His89
- Pocket volume: [X] ų
- Druggability: High/Medium/Low

---

## Alternative Structures

Ranked by quality and relevance:

| Rank | PDB ID | Resolution | Method | Ligands | Notes |
|------|--------|------------|--------|---------|-------|
| 1 | [4INS] | 1.9 Å | X-ray | Zn | Best resolution |
| 2 | [3I40] | 2.1 Å | X-ray | Zn, phenol | With inhibitor |
| 3 | [1TRZ] | 2.3 Å | X-ray | None | Porcine |

---





| Attribute | Value |
|-----------|-------|
|  | [uniprot1] | [PDBid]
 PDBe: https://www.ebi.ac.uk/pdbe/entry/pdb/[pdbid]

Retrieved: [date]

---

Quality Assessment Tiers

Experimental Structures

Tier	Symbol	Criteria
Excellent	●●●●	X-ray <1.5Å, complete, R-free <0.22
High	●●●○	X-ray <2.0Å OR Cryo-EM <3.0Å
Good	●●○○	X-ray 2.0-3.0Å OR Cryo-EM 3.0-4.0Å
Moderate	●○○○	X-ray >3.0Å OR NMR ensemble
Low	○○○○	>4.0Å, incomplete, or problematic

Resolution Guide

Resolution	Use Case
<1.5 Å	Atomic detail, H-bond analysis
1.5-2.0 Å	Drug design, mechanism studies
2.0-2.5 Å	Structure-based design
2.5-3.5 Å	Overall architecture, fold
>3.5 Å	Domain arrangement only

AlphaFold Confidence

pLDDT Score	Interpretation
>90	Very high confidence, experimental-like
70-90	Good backbone confidence
50-70	Uncertain, flexible regions
<50	Low confidence, likely disordered

---

Completeness Checklist

Every structure report MUST include:

For Specific PDB ID (Required)

• PDB ID and title
• Experimental method
• Resolution (or N/A for NMR)
• Organism
• Quality assessment
• Download links

For Protein Name Search (Required)

• Search summary with result count
• Top structures with quality ranking
• Best structure recommendation
• AlphaFold alternative (if no experimental structure)

Always Include

• Ligand information (or "No ligands bound")
• Data sources with links
• Retrieval date

---

Common Use Cases

Drug Discovery Target

User: "Get structure for EGFR kinase with inhibitor" → Filter for ligand-bound structures, emphasize binding site

Model Building

User: "Find best template for homology modeling of protein X" → High-resolution structures, note sequence coverage

Structure Comparison

User: "Compare available SARS-CoV-2 main protease structures" → All structures with systematic comparison table

AlphaFold When No Experimental

User: "Structure of protein with UniProt P12345" → Check PDB first, then AlphaFold, note confidence

---

Error Handling

Error	Response
"PDB ID not found"	Verify 4-character format, check if obsoleted
"No structures for protein"	Offer AlphaFold prediction, suggest similar proteins
"Download failed"	Retry once, provide alternative link
"Resolution unavailable"	Likely NMR/model, note in assessment

---

Tool Reference

RCSB PDB (Experimental Structures)

Tool	Purpose
search_structures_by_protein_name	Name-based search
get_protein_metadata_by_pdb_id	Basic info
get_protein_experimental_details_by_pdb_id	Method details
get_protein_resolution_by_pdb_id	Quality metric
get_protein_ligands_by_pdb_id	Bound molecules
download_pdb_structure_file	Coordinate files
get_similar_structures_by_pdb_id	Homologs

PDBe (European PDB)

Tool	Purpose
pdbe_get_entry_summary	Overview
pdbe_get_molecules	Molecular entities
pdbe_get_experiment_info	Experimental data
pdbe_get_binding_sites	Ligand pockets

AlphaFold (Predictions)

Tool	Purpose
alphafold_get_structure_by_uniprot	Get prediction
alphafold_search_structures	Search predictions