renkin 0.15.3

Ultra-fast retrosynthesis engine for computer-aided synthesis planning (CASP) — pure Rust, Python bindings via PyO3

RENKIN — Retrosynthesis Engine for Knowledge-Informed Navigation

Computer-Aided Synthesis Planning (CASP) · Pure Rust · WebAssembly · Python
Named after 錬金 (れんきん, renkin) — Japanese for alchemy: just as alchemists transformed base metals into gold, RENKIN transforms target molecules back into cheap starting materials.

日本語版 README · Documentation · Live Demo →

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What is RENKIN?

RENKIN is an open-source retrosynthesis engine for computer-aided synthesis planning (CASP) that automatically discovers optimal chemical reaction routes from a target molecule back to cheap, commercially available starting materials.

Built entirely in Rust with the chematic cheminformatics crate. Zero C/C++ dependencies. All crates enforce #![forbid(unsafe_code)] — compiler-verified Pure Safe Rust throughout.

→ Try the Live Playground — runs entirely in WebAssembly, no installation needed.
→ Full Documentation — API reference, examples, benchmark.

---

Installation

pip install renkin          # Python
cargo add renkin            # Rust
npm install renkin          # JavaScript / Node.js

---

Quick Start

import renkin

result = renkin.find_routes(
    "CC(=O)Oc1ccccc1C(=O)O",   # Aspirin
    depth=5,
    max_routes=3,
)

for route in result["routes"]:
    for step in route["steps"]:
        print(f"  {step['target']} → {' + '.join(step['precursors'])}  [{step['rule']}]")

import init, { find_routes } from './pkg/renkin.js';
await init();
const result = JSON.parse(find_routes("CC(=O)Oc1ccccc1C(=O)O", 5, 3, 0));

./target/release/renkin --target "CC(=O)Oc1ccccc1C(=O)O" --depth 5 \
    --templates data/templates_extracted_5000.smi --format tree

Target: CC(=O)Oc1ccccc1C(=O)O
Routes found: 3

Route 1  [score=1.02, depth=1]
OC(=O)c1ccccc1OC(=O)C
└── [extracted_169]
    ├── OC(=O)C  ✓ BB
    └── [OH]c1ccccc1C(=O)O  ✓ BB

Route 2  [score=1.02, depth=1]
OC(=O)c1ccccc1OC(=O)C
└── [extracted_145]
    ├── CC(=O)Cl  ✓ BB
    └── [OH]c1ccccc1C(=O)O  ✓ BB

Route 3  [score=1.03, depth=1]
OC(=O)c1ccccc1OC(=O)C
└── [extracted_238]
    ├── c1cccc(c1O)C(O)=O  ✓ BB
    └── C([OH])(=O)C  ✓ BB

Use --format mermaid for GitHub/Notion-compatible flowcharts.

---

Constraint-based Search

Restrict routes by the element composition of their building blocks.

Default search — all 5 routes for biphenyl:

renkin --target "c1ccc(-c2ccccc2)cc1" --templates data/templates_extracted_5000.smi --format tree

Routes found: 5
Route 1  [score=1.00, depth=1]  c1ccccc1Br + c1c(B(O)O)cccc1
Route 2  [score=1.03, depth=1]  c1ccccc1Br + c1c(B(O)O)cccc1
Route 3  [score=1.06, depth=1]  c1cc(Cl)ccc1 + c1c(B(O)O)cccc1
Route 4  [score=1.08, depth=1]  c1(I)ccccc1  + c1c(B(O)O)cccc1
Route 5  [score=1.08, depth=1]  c1ccccc1Br  + c1(B2OC(C(C)(C)O2)(C)C)ccccc1

Constrained search — boronic-acid coupling, no Br or I starting materials:

renkin --target "c1ccc(-c2ccccc2)cc1" --templates data/templates_extracted_5000.smi \
    --require-elements "B" --avoid-elements "Br,I" --format tree

Routes found: 1

Route 1  [score=1.06, depth=1]
c1ccccc1-c2ccccc2
└── [extracted_398]
    ├── c1cc(Cl)ccc1  ✓ BB
    └── c1c(B(O)O)cccc1  ✓ BB

Constraints compose freely and are enforced in two layers:

• --avoid-elements prunes expansions during search when a BB precursor contains a forbidden element (no dead-end nodes added to the heap).
• A final route-level post-filter is still applied for correctness.
• --require-elements is a route-level post-filter only.

Add --verbose to print search statistics (nodes expanded, elapsed time) to stderr. Performance counters are available in native builds only; disabled in WASM.

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Key Features

Feature	Detail
Pure Safe Rust	#![forbid(unsafe_code)] on all crates — compiler-enforced, zero C/C++ dependencies
A* / AND-OR Tree Search	Retro*-equivalent algorithm with pluggable heuristics (MoleculeValueEstimator, ReactionPrior)
Up to 50k reaction templates	Auto-extracted from USPTO-50k/MIT via rdchiral; frequency-weighted priority; --templates for custom sets
Route scoring	confidence, step_confidence, success_probability (Retro-prob style), convergency, atom_economy per step
Route cost scoring	route_cost = Σ(BB cost) + steps×0.5; actual prices via --bb-prices CSV
Forward validation	renkin-forward validate verifies each step by applying templates forward; accepts --route-json or stdin
PaRoutes benchmark	renkin-bench --input-format paroutes for multi-step ground-truth evaluation with depth_delta and route_diversity
Atom balance check	renkin-bench flags steps where target_MW > Σ precursor_MW (CompleteRXN reference)
Procedure hints	19 hand-crafted rules carry procedure_hint — placeholder for QFANG-style procedure generation
MCP server	renkin-mcp exposes find_routes, validate_route, estimate_diversity to Claude Desktop
Beam search	--beam-width N for memory-bounded exploration; SmallVec<[FEntry; 6]> stack-allocated frontier
Parallel rule application	rayon on non-WASM; sequential fallback on wasm32
tract-onnx NN scorer	Pure Rust ONNX inference (no C++ dep) — optional --scorer flag for Phase B template relevance scoring
Route visualization	--format tree ASCII tree · --format mermaid GitHub/Notion flowchart
building_blocks in JSON	Each route includes the leaf starting-material SMILES — no manual step parsing needed
MCP server	renkin-mcp binary — AI agents (Claude, etc.) call retrosynthesis over JSON-RPC stdio
Tetrahedral stereo @/@@	Full stereochemistry support via chematic 0.4.16
Python	pip install renkin — pre-built wheels for Linux/macOS/Windows
WASM	~500 KB bundle — runs in the browser at near-native speed
509 building blocks	Aryl halides, boronic acids, heterocycles, amines, acids, amino acids

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Pipeline Examples

# Route cost scoring with commercial prices
renkin -t "Cc1ccc(-c2ccccc2)cc1" --bb-prices data/prices.csv --format json

# Forward validation — pipe find_routes output directly
renkin -t "CC(=O)Oc1ccccc1C(=O)O" --format json | renkin-forward validate

# Faster template retrieval with bond-center index (~24% speedup)
renkin -t "c1ccc(NC(=O)c2ccccc2)cc1" --templates data/templates_extracted_5000.smi --bond-index

---

Benchmark

USPTO-50k test set (4,907 molecules, full evaluation):

Evaluation definition: A molecule is solved if find_routes returns at least one route whose leaf precursors are all in the 509-reagent building block set, within depth=5 and beam=100. Ground-truth reactants from USPTO-50k are not checked — any commercially accessible route counts.

Evaluation note: All numbers use the standard USPTO-50k train/test split (same corpus). Templates are extracted from the training set and evaluated on the test set. Numbers reflect performance within the USPTO-50k domain; out-of-distribution generalization is separately evaluated via ChEMBL approved drugs (81.8%, 409/500).

Config	Solved	Rate	BBs	Templates	depth	beam	ms/mol
v0.1.0 initial	366/4907	7.5%	463	31	3	50	—
+ auto templates (top-300)	1363/4907	27.8%	463	222	3	50	—
+ depth=5, top-500 templates	2315/4907	47.2%	463	314	5	50	—
+ beam=100	2688/4907	54.8%*	463	314	5	100	—
+ Phase A (template freq. weighting)	3540/4907	72.1%†	463	314	5	100	—
+ 5,000 templates, 480 BBs	3826/4907	78.0%	480	5,000	5	100	2,775
Phase A unlimited (beam=0)	3832/4907	78.1%	480	5,000	5	0	—
Phase B (NN scorer, tract-onnx)	3826/4907	78.0%	480	5,000	5	100	3,394
+ diaryl sulfone rule, 509 BBs	3831/4907	78.1%	509	5,000	5	100	≈2,800

* 29/50 chunks, previous binary
† 50/50 chunks — 72.1% (3,540/4,907) confirmed

Under RENKIN's evaluation setting (see definition above), RENKIN reaches 78.1% on USPTO-50k. Published numbers for AiZynthFinder (45–53%), Retro* (44.3%), and ASKCOS (41%) use different stock databases, template counts, and evaluation years — this is not a matched-condition comparison.
Note: LocalRetro (53.4%) and GLG (58.0%) report single-step top-1 prediction accuracy — a different metric, not directly comparable.
Full benchmark details →

Benchmark scope note: USPTO-50k is used here as a standardized sanity benchmark, not as proof of broad real-world synthesis performance. The corpus covers a narrow slice of reaction space (primarily C–C and C–N bond formations common in pharmaceutical synthesis), and reaction types with sparse USPTO representation are systematically underserved. Out-of-distribution performance on ChEMBL approved drugs (81.8%, 409/500) suggests the rule set generalizes beyond the test corpus, but neither number should be interpreted as a guarantee of route quality on arbitrary targets.

PaRoutes compatibility

RENKIN is compatible with the PaRoutes multi-step benchmark. Download their stock compounds and target molecules, then pass them directly:

renkin-bench \
  --input paroutes_n1_targets.smi \
  --building-blocks paroutes_stock.smi \
  --templates data/templates_extracted_5000.smi \
  --depth 5 --beam-width 100

The JSON output includes avg_nodes_expanded, avg_confidence, avg_convergency, and avg_success_prob (Retro-prob style) alongside the standard solved/success_rate metrics.

---

Competitive Landscape

Tool	Language	License	WASM	Zero-dep	Algorithm	Template source	Stock
ASKCOS	Python	CC BY-NC	No	No (Docker, 64 GB)	MCTS + A*	USPTO (ML)	ZINC
AiZynthFinder	Python	MIT	No	No (conda + model)	MCTS	USPTO (ML, ~50k)	eMolecules (~6M)
SYNTHIA	Closed	Proprietary	No	No	SMARTS + AND/OR	Manual curated	Sigma-Aldrich
IBM RXN	Closed	Cloud SaaS	No	No	Transformer	USPTO	—
Retro*	Python	MIT	No	No (unmaintained)	A* + AND/OR	USPTO (ML)	eMolecules
★ RENKIN	Rust	MIT	Yes	Yes	A* + AND/OR	Hand-curated + rdchiral (5k default; 50k via --templates)	509+

RENKIN's goal: match state-of-the-art accuracy using only curated rules and auto-extracted SMIRKS templates — no GPU, no training data, no black boxes. Under RENKIN's benchmark setting, it reaches 78.1% (3,831/4,907 — full run confirmed). Template frequency weighting (Phase A) combined with 5,000 auto-extracted templates and 509 building blocks delivers this result. RENKIN runs anywhere: browser, CLI, Python — single cargo build.

⚠️ The table above lists tools under different evaluation conditions. No matched-condition experiment against other tools has been performed.

---

MCP Server

renkin-mcp exposes retrosynthesis as an MCP tool so AI agents (Claude, etc.) can call it directly.

Setup — add to claude_desktop_config.json:

{
  "mcpServers": {
    "renkin": { "command": "/path/to/renkin-mcp" }
  }
}

Tool: find_routes(smiles, depth?, max_routes?, avoid_elements?, require_elements?)

The server auto-detects data/building_blocks.smi and data/templates_extracted_5000.smi in the working directory. Falls back to the embedded 509-BB / 20-rule defaults if not found.

cargo build --release
# binary: target/release/renkin-mcp

---

Architecture

Workspace scope

┌──────────────────────────────────────────────────────────────────┐
│ renkin workspace (this repository)                               │
│                                                                  │
│  renkin  (retrosynthesis)         renkin-forward  (planned)      │
│  ──────────────────────           ─────────────────────────────  │
│  target → precursors              reactants → products           │
│  A* / AND-OR search               template-based forward         │
│  route scoring & constraints      (validates retro routes)       │
│        │                                    │                    │
│        └──────────────────┬─────────────────┘                    │
│                           ▼                                      │
│               chematic  (molecular representation,               │
│               SMILES, substructure matching, reaction SMARTS)    │
└──────────────────────────────────────────────────────────────────┘

Internal data flow (renkin crate)

Target SMILES
     │
     ▼
┌─────────────────────────┐
│     chem_env.rs         │  ← chematic wrapper
│  - SMILES parse         │     canonical-SMILES FxHashSet BB lookup (O(1))
│  - 20 built-in + up to 50k via --templates  │     fragment sanitization + ring-leak filter
│  - Building block check │     apply_retro memoization cache
└────────────┬────────────┘
             │  par_iter (rayon / sequential on WASM)
             ▼
┌─────────────────────────┐
│      search.rs          │  ← A* / AND-OR Tree Search
│  - Priority queue       │     SA Score heuristic + memoization
│  - Closed list          │     beam search (SmallVec frontier)
│  - Arc<PathNode> paths  │     O(1) path sharing per child
└────────────┬────────────┘
             │
             ▼
┌─────────────────────────┐
│      score.rs           │  ← Heuristic / Cost Function
│  - SA Score (chematic)  │     h = Σ(1 + 0.5·(sa−1)/9)
│  - MW step cost         │     g = Σ(1 + total_mw/2000)
└────────────┬────────────┘
             │
             ▼
┌─────────────────────────┐   (optional)
│      scorer.rs          │  ← Phase B: NN Template Scorer
│  - tract-onnx           │     Pure Rust ONNX inference
│  - --scorer flag        │     molecule-specific template ranking
└────────────┬────────────┘
             │
             ▼
  JSON  ←  CLI / Python / WASM

---

Project Structure

renkin/                          ← Cargo workspace root (planned)
├── Cargo.toml
├── src/                         ← renkin crate (retrosynthesis)
│   ├── lib.rs                   # public library
│   ├── main.rs                  # CLI binary  (--templates, --scorer flags)
│   ├── bin/benchmark.rs         # renkin-bench binary  (--templates flag)
│   ├── chem_env.rs              # retro rules + BB lookup + template loader
│   ├── score.rs                 # SA Score heuristic + step cost
│   ├── search.rs                # A* / AND-OR tree engine + beam pruning
│   ├── scorer.rs                # Phase B: tract-onnx NN template scorer
│   ├── python.rs                # PyO3 bindings (--features python)
│   └── wasm.rs                  # wasm-bindgen bindings (cfg = wasm32)
├── crates/                      ← sibling crates (in development)
│   └── renkin-forward/          # forward reaction prediction (reactants → products)
├── data/
│   ├── building_blocks.smi              # 509 curated commercial starting materials
│   ├── templates_extracted_5000.smi     # 5,000 auto-extracted SMIRKS templates
│   ├── benchmark_targets.smi            # internal benchmark set
│   └── bench_chunks/                    # USPTO-50k per-chunk results
├── scripts/
│   ├── extract_templates.py         # rdchiral template extraction pipeline
│   └── run_benchmark_chunks.sh      # resumable chunked benchmark runner
├── docs/                # MkDocs source → kent-tokyo.github.io/renkin/
└── mkdocs.yml

---

Roadmap

• Route cost scoring — route_cost field + --bb-prices path.csv flag (SA Score proxy or real prices)
• Cargo workspace — crates/renkin-forward/ sibling crate
• renkin-forward predict — template-based forward prediction (reactants → products)
• renkin-forward validate — forward-validate retrosynthetic routes; stdin-pipe friendly

Completed milestones

• SMIRKS retro-reaction rules + fragment sanitization
• A* / AND-OR tree search, closed list, degenerate-route filter
• SA Score heuristic + beam search
• Parallel rule application (rayon; sequential fallback on WASM)
• Python bindings (PyO3 + maturin) · pip install renkin
• WASM build · npm install renkin
• Benchmark CLI (renkin-bench) + USPTO-50k evaluation
• WASM browser playground + i18n (EN/JA/ZH)
• Graph-based biaryl cleavage · O(1) canonical-SMILES BB index
• Published to crates.io / PyPI / npm · GitHub Actions CI/CD
• MkDocs documentation site · GitHub Pages playground
• Auto template extraction (rdchiral): 27.8% → 78.1% USPTO-50k
• Tetrahedral stereo @/@@ + E/Z double-bond stereo
• Template frequency weighting (Phase A): 72.1% USPTO-50k
• FxHashMap · SmallVec beam frontier · SA Score memoization · Arc path sharing
• 5,000 extracted templates + 509 BBs: 78.1% USPTO-50k (3,831/4,907 ✅)
• NN template scorer via --scorer flag (tract-onnx, Pure Rust ONNX)
• --format tree|mermaid route visualization
• Constraint-based search: --avoid-elements, --require-elements
• --verbose search statistics to stderr
• MCP server (renkin-mcp) — AI agents call retrosynthesis directly
• #![forbid(unsafe_code)] — compiler-enforced Pure Safe Rust

---

Citation

If you use RENKIN in academic work, please cite:

@software{renkin2026,
  author    = {kent-tokyo},
  title     = {{RENKIN}: Retrosynthesis Engine for Knowledge-Informed Navigation},
  year      = {2026},
  url       = {https://github.com/kent-tokyo/renkin/releases/tag/v0.15.2},
  version   = {0.15.2},
  license   = {MIT}
}

---

License

MIT

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GitHub Topics: retrosynthesis cheminformatics wasm rust drug-discovery casp synthesis-planning computational-chemistry