synomega 0.2.0

Retrosynthesis toolkit: single-step prediction, multi-step route planning, synthesizability scoring

synomega

A retrosynthesis toolkit that turns a target molecule into synthesis routes and a continuous synthesizability score. Three decoupled layers:

synthesizability   is this target reachable from purchasable material, in N steps?
     ↑
search             Retro* / MCTS / best-first over an AND-OR graph
     ↑
single-step        product SMILES -> ranked reactant candidates

The layers meet at a deliberately narrow interface — a single-step backend only implements predict(smiles, top_k) -> [Prediction] — so the planner and the scorer do not care whether predictions come from a graph neural network, a transformer, or plain template matching.

Installation

pip install synomega           # core: rdkit + numpy
pip install "synomega[gnn]"    # + the D-MPNN neural single-step backend (torch)

The neural backend is an optional extra on purpose: the template-rule backend runs anywhere, with no GPU and no PyTorch. Requires Python ≥ 3.10.

Quick start

from synomega import Planner, SynthesizabilityScorer
from synomega.singlestep import TemplateGNN
from synomega.stock import InMemoryStock

model   = TemplateGNN.from_pretrained("path/to/model_run")   # a trained checkpoint
stock   = InMemoryStock.from_keys_file("building_blocks.keys.gz")
planner = Planner(model, stock, algorithm="retrostar")

result = planner.plan("CC(=O)Nc1ccccc1", max_depth=5, time_limit=60)
print(result.solved)
print(result.best_route.describe())

target: CC(=O)Nc1ccccc1
solved: True  steps: 2  depth: 2  bb_coverage: 1.00
  [1] CC(=O)O.Nc1ccccc1>>CC(=O)Nc1ccccc1  (score=0.4348)
  [2] O=[N+]([O-])c1ccccc1>>Nc1ccccc1     (score=0.2174)

Synthesizability scoring

scorer = SynthesizabilityScorer(planner)

r = scorer.score("CC(=O)Nc1ccccc1", max_steps=5)
r.solved            # True — a complete route to purchasable material exists
r.bb_coverage       # 1.0 — fraction of the best route's leaves that are buyable
r.min_steps         # 2  — reactions in the shortest solved route
r.min_route_depth   # 2  — longest linear sequence of that route

report = scorer.score_batch(targets, max_steps=5)
report.solve_rate         # fraction of targets solved
report.mean_bb_coverage
report.to_dataframe()

Excluding the target from stock. A molecule that is itself a catalogue item is otherwise "solved" in zero steps. Pass exclude_target=True to force a real disconnection — the target is treated as not purchasable, while its intermediates still are. Available on both planning and scoring (default off):

planner.plan("CC(=O)Nc1ccccc1O", exclude_target=True)
scorer.score("CC(=O)Nc1ccccc1O", max_steps=5, exclude_target=True)

Two synthesizability metrics

These are conflated in the literature; synomega keeps them apart because they answer different questions.

Metric	Meaning	Use it for
solved@N / solve_rate	Binary — does a route of depth ≤ N exist whose leaves are all purchasable?	Comparing against published numbers
bb_coverage@N	Continuous — fraction of the best route's leaves that are purchasable	Ranking molecules by how close they are

bb_coverage matters because most targets are unsolved at realistic step limits. A 5-step route with 4 of 5 leaves buyable scores 0.8, not 0 — so a near-miss is distinguishable from a total failure, and a set of molecules can be ranked rather than merely split into solved/unsolved.

Search algorithms

Algorithm	Character	When to use
retrostar	Expands the frontier molecule with the lowest estimated total route cost (Chen et al. 2020)	Default
mcts	UCT with greedy rollouts; tolerant of an unreliable top-1	Weak single-step model
bfs	Best-first on g + h	Baseline / debugging

All three share the AND-OR graph, the budget, and the route extractor, so their results are directly comparable.

Command line

# one-time: precompute building-block InChIKeys so later loads take seconds
synomega build-stock --catalogue catalogue.smi.gz --out building_blocks.keys.gz

synomega plan  --target "CC(=O)Nc1ccccc1" --model path/to/model_run \
               --stock building_blocks.keys.gz --stock-is-keys --max-steps 5

synomega score --targets targets.smi --model path/to/model_run \
               --stock building_blocks.keys.gz --stock-is-keys \
               --max-steps 5 --out report.json

Bring your own single-step model

Any object implementing the SingleStepModel interface plugs into the planner:

from synomega.singlestep import SingleStepModel, Prediction

class MyModel(SingleStepModel):
    name = "my-model"
    def predict(self, smiles: str, top_k: int = 50) -> list[Prediction]:
        # return candidate disconnections, best first
        return [Prediction(reactants=("CCO", "CC(=O)O"), score=0.9)]

planner = Planner(MyModel(), stock, algorithm="retrostar")

Built-in backends: TemplateGNN (D-MPNN template classifier, needs [gnn]) and TemplateRuleModel (pure template matching, no PyTorch).

Design notes

• AND-OR graph, not a tree. A molecule is solved if it is in stock or any of its reactions is solved; a reaction is solved if all its reactants are. Molecules are interned by InChIKey, so an intermediate reached down two branches is one node, expanded once. Cycles are rejected at edge creation.
• Batched expansion. The search pulls a batch of frontier molecules and issues one predict_batch, so a GPU-backed model is not left idle.
• Caching. Planner(cache=True) (default) memoizes expansions; cache_path= persists them to SQLite across runs.
• Stock membership is by InChIKey, matching a vendor catalogue written by a different toolkit. There is deliberately no Bloom-filter backend — false positives would inflate solve-rate and break comparability with published numbers.

Development

git clone https://github.com/zbc0315/synomega
cd synomega
pip install -e ".[gnn,dev]"
pytest

License

MIT — see LICENSE.