HEDGEHOG

Hierarchical Evaluation of Drug GEnerators tHrOugh riGorous filtration

HEDGEHOG is a comprehensive benchmark pipeline for evaluating generative models in molecular design. It takes a set of generated SMILES strings and progressively filters them through physicochemical descriptors, structural alerts, synthetic accessibility checks, molecular docking, and post-docking pose analysis — producing a detailed HTML report with per-stage statistics, interactive visualizations, and generative quality metrics.

Pipeline Structure

Key Features

7-stage evaluation pipeline — molecules pass through Mol Prep (Datamol standardization), descriptors, structural filters, synthesis evaluation, docking, docking filters, and final descriptor recalculation.
11 structural filters — common alerts (PAINS, Glaxo, BMS, Dundee), molecular graph severity, molecular complexity, NIBR, Bredt rule, Lilly MedChem rules, plus 5 medicinal chemistry filters (protecting groups, ring infraction, stereo center, halogenicity, symmetry).
Retrosynthesis analysis — synthetic accessibility scoring with SA Score, SYBA, and full retrosynthetic route analysis via AiZynthFinder.
Molecular docking — binding affinity scoring and pose generation with SMINA, GNINA, and/or Matcha, followed by pose quality filtering.
Automated reporting — interactive HTML report with molecule retention funnel, descriptor distributions (with reference threshold lines), filter breakdowns, docking results, and MolEval generative metrics.
CLI and TUI interfaces — a Typer-based command-line interface (hedgehog / hedge) for scripted workflows, plus an interactive terminal UI built with Node.js for visual configuration and pipeline management.

Quick Example


git clone https://github.com/LigandPro/hedgehog.git
cd hedgehog
uv sync
 
# First safe run: descriptors + structural filters only
uv run hedgehog --stage descriptors --stage struct_filters --force-new

This smoke run avoids docking and retrosynthesis. For the full pipeline, install AiZynthFinder and make sure the selected docking tools, receptor, and reference ligand paths are valid:


uv run hedgehog setup aizynthfinder
uv run hedgehog --auto-install