Overview

Protein structure retrieval and ligand docking agent for the PharmaClaw drug discovery pipeline. Fetches experimental structures from RCSB PDB and predicted structures from AlphaFold DB, detects binding sites, and performs conformer-based docking with RDKit.

Quick Start

# Fetch structure and dock a ligand
python scripts/alphafold_agent.py '{"uniprot": "P01116", "smiles": "CC(=O)Nc1ccc(O)cc1"}'
# Structure retrieval only
python scripts/alphafold_agent.py '{"uniprot": "P01116"}'

Capabilities

Feature	Method	Source
Structure Fetch	RCSB Search API + AlphaFold DB	Public PDB files
Fold Prediction	ESMFold via HuggingFace	Sequence → 3D structure
Binding Sites	Pocket detection	Residue-level pockets
Ligand Docking	RDKit conformer generation	SMILES → affinity score

Decision Tree

• UniProt ID provided? → Fetch from RCSB PDB / AlphaFold DB
• FASTA sequence provided? → Predict fold via ESMFold
• SMILES provided? → Dock ligand into detected binding pocket
• No structure found? → Fall back to ESMFold prediction

Input Format

{
  "uniprot": "P01116",
  "smiles": "CC(=O)Nc1ccc(O)cc1",
  "fasta": "path/to/sequence.fasta"
}

Output Format

{
  "pdb": "1abc.pdb",
  "sites": [{"res": "G12", "pocket_vol": 150}],
  "docking": {"affinity": -15.2, "viz": "docked.png"},
  "compliance": "Public AlphaFold 2 DB/ESMFold (commercial OK)"
}

Chain Integration

• Receives from: Chemistry Query (SMILES for docking), Literature (target proteins)
• Feeds into: IP Expansion (novel binding modes), Catalyst Design (structure-guided synthesis)

Dependencies

• rdkit-pypi — Conformer generation and molecular descriptors
• biopython — PDB parsing and FASTA sequence handling
• requests — API calls to RCSB and AlphaFold DB

Compliance

Uses only publicly available protein structures (RCSB PDB, AlphaFold DB) and open-source prediction (ESMFold). All data sources are commercially permissible. No proprietary AlphaFold 3 server calls.

Scripts

• scripts/alphafold_agent.py — Main agent: fetch, predict, detect sites, dock

Limitations

• Docking uses RDKit conformer scoring (not full physics-based docking like Vina)
• ESMFold prediction requires significant compute for large proteins
• Binding site detection is simplified; production use should integrate fpocket or P2Rank

# Fetch structure and dock a ligand
python scripts/alphafold_agent.py '{"uniprot": "P01116", "smiles": "CC(=O)Nc1ccc(O)cc1"}'
# Structure retrieval only
python scripts/alphafold_agent.py '{"uniprot": "P01116"}'

{
  "uniprot": "P01116",
  "smiles": "CC(=O)Nc1ccc(O)cc1",
  "fasta": "path/to/sequence.fasta"
}

{
  "pdb": "1abc.pdb",
  "sites": [{"res": "G12", "pocket_vol": 150}],
  "docking": {"affinity": -15.2, "viz": "docked.png"},
  "compliance": "Public AlphaFold 2 DB/ESMFold (commercial OK)"
}