pharmaclaw-alphafold-agent

Compliant AlphaFold Agent for protein structure retrieval, ESMFold prediction, binding site detection, and RDKit ligand docking. Fetches public PDB/AlphaFold DB structures, predicts folds via ESMFold (HuggingFace), identifies binding pockets, and performs basic molecular docking. Chains from Chemistry Query (receives SMILES for docking) and feeds into IP Expansion and Catalyst Design. Triggers on alphafold, fold, PDB, docking, structure, protein, binding site, pocket, UniProt, KRAS, target.

PharmaClaw AlphaFold Agent

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