molcore-chem

AI-native cheminformatics toolkit — Rust-accelerated fingerprints and PyG conversion, with full RDKit compatibility and a built-in MCP server.

pip install molcore-chem

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Overview

molcore extends RDKit workflows rather than replacing them. The hot paths — fingerprint generation and PyTorch Geometric graph conversion — are rewritten in Rust using Rayon parallelism and zero-copy array transfer, while standardization, descriptors, and scaffold splitting delegate to RDKit through an isolated bridge layer.

Capability	Implementation	Notes
ECFP4 fingerprints	Rust (Rayon + u64 bit-packing)	35–132× faster than RDKit
PyG graph conversion	Rust (IntoPyArray → torch.from_numpy)	4.3× faster, zero-copy
Tanimoto matrix	Rust (Rayon + popcount)	4.3–29× faster at scale
Standardization, descriptors, scaffold split	RDKit (via rdkit_bridge.py)	Parity speed, cleaner API

---

Quickstart

from molcore.molecule import Mol
from molcore.pipeline import featurize_smiles
from molcore.predictor import PropertyPredictor
from molcore.io import MolDataset
import numpy as np

# Parse — immutable, Rust-backed
mol = Mol.from_smiles("CC(=O)Oc1ccccc1C(=O)O")   # aspirin
data = mol.to_pyg()                                # PyG Data, zero-copy, 9 node features

# Batch fingerprints — Rust Rayon parallel
fps = featurize_smiles(smiles_list, backend="rust")   # (N, 2048) uint8 Tensor

# Full dataset pipeline
ds = MolDataset.from_smiles(smiles_list, compute_fps=True, compute_desc=True)
ds.labels = np.array(logp_values, dtype=np.float32)
train_ds, val_ds, test_ds = ds.scaffold_split()

# Train GCN with MC Dropout uncertainty
pred = PropertyPredictor(hidden=64, epochs=100)
pred.fit(train_ds, val_dataset=val_ds)
means, stds = pred.predict_with_uncertainty(["CCO", "c1ccccc1"], n_samples=30)

Open in Colab →

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Benchmarks

All numbers on Apple M-series (arm64), CPU-only, Python 3.12.

ECFP4 Fingerprints

Batch size	molcore (Rust)	RDKit	Speedup
1 000 SMILES	1.3M mol/s	14 800 mol/s	88×
10 000 SMILES	2.0M mol/s	15 100 mol/s	132×

Tanimoto Similarity Matrix

Query × Library	molcore (Rust)	RDKit BulkTanimoto	Speedup
50 × 1 000	31M pairs/s	7.3M pairs/s	4.3×
500 × 10 000	224M pairs/s	7.7M pairs/s	29×

End-to-End Pre-training Pipeline (500 molecules)

Step	molcore	RDKit	Speedup
Standardize	242 ms	225 ms	~parity
ECFP4 fingerprints	1.1 ms	37.3 ms	35×
7 Lipinski descriptors	124 ms	114 ms	~parity
Scaffold split	33 ms	35 ms	~parity
PyG conversion (200 mols)	3.3 ms	14.4 ms	4.3×

GNN Property Prediction — ESOL Solubility

ESOL dataset (Delaney 2004, 1128 molecules), scaffold split. Scaffold split is substantially harder than the random split used in published MoleculeNet baselines — results are not directly comparable to the published RMSE ≈ 0.58.

Configuration	RMSE	R²
GCN, hidden=64, 3 layers, 300 epochs	1.038	0.727
Optuna-tuned (30 trials): hidden=128, 4 layers	1.090	0.709

---

Features

Billion-Scale Streaming Screen

Screen libraries that do not fit in RAM using any Iterable[str] of SMILES — file iterators, database cursors, or generators. Peak memory is O(chunk_size × nbits/8).

from molcore.streaming import stream_screen, StreamingScreen

def from_file(path):
    with open(path) as fh:
        for line in fh:
            yield line.strip().split()[0]

# Tanimoto similarity + SMARTS filter in a single pass
hits = stream_screen(
    from_file("chembl_34.smi"),
    query="c1ccc(N)cc1",
    query_smarts="[NH2]",
    threshold=0.4,
    chunk_size=10_000,
    progress=True,
)
for smiles, tanimoto_score in hits:
    print(smiles, tanimoto_score)

# Stateful version — screen multiple chunks, inspect running stats
screen = StreamingScreen(query="c1ccc(N)cc1", threshold=0.4)
for chunk in my_chunks:
    chunk_hits = screen.screen_chunk(chunk)
    save_hits(chunk_hits)
print(screen.stats)  # {n_screened, n_hits, hit_rate, elapsed_s, rate_mol_s}

MCP Server

Any MCP-compatible host (Claude Desktop, Continue, Cursor) can invoke molcore tools directly without a local Python installation.

molcore mcp                                    # stdio transport
molcore mcp --transport http --port 8765       # HTTP transport

Claude Desktop — add to claude_desktop_config.json:

{
  "mcpServers": {
    "molcore": {
      "command": "python",
      "args": ["-m", "molcore.mcp_server"],
      "env": {}
    }
  }
}

Nine tools are exposed: featurize, screen_smarts, screen_similarity, admet_screen, synthesizability, generate, retro_score, active_suggest, and pareto_optimize.

SDF and Parquet I/O

from molcore.io import MolDataset

ds = MolDataset.from_sdf("library.sdf")
ds = MolDataset.from_sdf("library.sdf", compute_fps=True, compute_desc=True)
ds.write_sdf("output.sdf")
ds.write_parquet("library.parquet")           # Arrow columnar, snappy-compressed
ds2 = MolDataset.read_parquet("library.parquet")

Pandas Integration

import molcore.pandas_tools as mpt

df = mpt.load_sdf("library.sdf")                  # DataFrame with 'Mol' + 'smiles' columns
df = mpt.add_descriptors(df, preset="lipinski")   # MolWt, LogP, TPSA, HBD, HBA, …
df = mpt.add_fingerprints(df, kind="ecfp4")       # adds 'fp' column
df = mpt.filter_by_smarts(df, "c1ccncc1")         # substructure filter in-place
df = mpt.standardize_smiles(df)                   # strip salts → neutralize → canonical tautomer

Descriptors

from molcore.rdkit_bridge import calc_named_descriptors

arr, names = calc_named_descriptors(smiles, preset="lipinski")   # 7 descriptors
arr, names = calc_named_descriptors(smiles, preset="druglike")   # 15 descriptors
arr, names = calc_named_descriptors(smiles, preset="all")        # ~200 descriptors
arr, names = calc_named_descriptors(smiles, names=["MolWt", "TPSA", "BertzCT"])

Returns (N, D) float32 arrays.

Fingerprint Types

fps = featurize_smiles(smiles, kind="ecfp4")                # (N, 2048) — Rust parallel
fps = featurize_smiles(smiles, kind="maccs")                # (N, 167)
fps = featurize_smiles(smiles, kind="atom_pairs")           # (N, 2048)
fps = featurize_smiles(smiles, kind="topological_torsions") # (N, 2048)
fps = featurize_smiles(smiles, kind="rdkit")                # (N, 2048) RDKit path-based

2D Depiction

mol = Mol.from_smiles("CC(=O)Oc1ccccc1C(=O)O")
mol              # renders inline in Jupyter via _repr_svg_
mol.to_png("aspirin.png")

ds = MolDataset.from_sdf("library.sdf")
ds               # renders 8-molecule grid inline
ds.draw_grid(n=20, mols_per_row=4)

Standardization

from molcore.rdkit_bridge import standardize

clean = standardize("[Na+].OC(=O)c1ccccc1")   # → "OC(=O)c1ccccc1"
# strips salts → neutralizes charges → canonical tautomer → canonical SMILES

MCS and R-Group Decomposition

from molcore.rdkit_bridge import find_mcs, rgroup_decompose

smarts = find_mcs(["CC(=O)Oc1ccccc1", "CC(=O)Oc1ccc(F)cc1", "CC(=O)Oc1ccc(Cl)cc1"])

rows = rgroup_decompose("c1ccc([*:1])cc1", smiles_list)
# → [{"Core": "c1ccccc1", "R1": "F"}, {"Core": "c1ccccc1", "R1": "Cl"}, ...]

GCN Predictor with MC Dropout Uncertainty

from molcore.predictor import PropertyPredictor

pred = PropertyPredictor(hidden=64, n_layers=3, epochs=100, dropout=0.1)
pred.fit(train_ds, val_dataset=val_ds, verbose=True)

predictions = pred.predict(smiles_list)                          # numpy array
means, stds = pred.predict_with_uncertainty(smiles_list, n_samples=30)

pred.save("logp_model.pt")
pred2 = PropertyPredictor.load("logp_model.pt")

Drug-Target Interaction Prediction

from molcore import DTIDataset, DTIPredictor

ds = DTIDataset(
    smiles    = ["CC(=O)O",    "c1ccccc1"],
    sequences = ["MKTLLILAVL", "ACDEFGHIKL"],
    labels    = [6.5,           7.2],          # pIC50
)

train, val, test = ds.scaffold_split(train_frac=0.8, val_frac=0.1)

pred = DTIPredictor(hidden=64, n_layers=3, epochs=100, model_type="gcn")
pred.fit(train, val_dataset=val)

affinities = pred.predict(["CCO"], ["MKTLLILAVL"])   # (N,) float32 pIC50
metrics    = pred.score(test)                         # {r2, mae, rmse, n}

model_type accepts "gcn", "gat", or "gin". ESM-2 protein embeddings are available via pip install molcore-chem[bio].

---

Installation

pip install molcore-chem

Requires Python 3.11+. RDKit and PyTorch are declared dependencies — no manual conda setup required. Pre-compiled Rust extensions are included in the wheel.

GPU (CUDA 12.1):

pip install molcore-chem
pip install torch --index-url https://download.pytorch.org/whl/cu121

Build from Source

git clone https://github.com/Anteneh-T-Tessema/molcore
cd molcore
./setup_dev.sh    # creates .venv, builds Rust extension, runs tests
source .venv/bin/activate

Requires Rust 1.70+:

curl --proto '=https' --tlsv1.2 -sSf https://sh.rustup.rs | sh

---

Architecture

SMILES strings
  │
  ▼  Rust ingest (RDKit-backed aromaticity perception)
  │  — sanitize, kekulize, ring perception, implicit H
  ▼
petgraph StableGraph (immutable after construction)
  │
  ├─▶ ecfp4_batch()          → (N × 2048) uint8  ─▶ torch.from_numpy()  ─▶ Tensor
  │   Rayon parallel · u64 bit-pack · hardware popcount · 35–132× faster
  │
  ├─▶ mol_to_graph_arrays()  → node_feats (9-dim), edge_index, edge_attr ─▶ PyG Data
  │   Zero-copy IntoPyArray · 4.3× faster than manual Python construction
  │
  └─▶ tanimoto_matrix()      → (Q × L) float32
      Rayon parallel · u64 popcount · 29× faster at scale

Python layer (molcore/)
  molecule.py      — frozen Mol dataclass (FrozenInstanceError on mutation)
  pipeline.py      — featurize_smiles() batch-first entry point
  rdkit_bridge.py  — all RDKit calls isolated here (one file to update)
  io.py            — MolDataset: SDF + Parquet + DataFrame bridge
  predictor.py     — PropertyPredictor: 3-layer GCN + MC Dropout
  dti.py           — DTIPredictor: GCN/GAT/GIN ligand + 1D-CNN protein encoder
  pandas_tools.py  — DataFrame-first API for existing RDKit workflows
  agentic_rag.py   — ChemRAG: iterative chemical literature retrieval

Design Invariants

1. Mol is always immutable — transforms return new instances.
2. RDKit is never in hot paths — all RDKit calls are isolated to rdkit_bridge.py.
3. All Rust→Python array transfers use IntoPyArray — no Python-side copy loops.
4. Batch API is primary — per-molecule methods are convenience wrappers.
5. Backend flags are explicit — "rust" or "rdkit" is always caller-supplied.

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Development

maturin develop --release --features extension-module   # build Rust extension
cargo test -p molcore-core                              # Rust unit tests
pytest tests/ evals/ -q                                 # 1061 Python/eval tests
python benchmarks/prove_scale.py                        # throughput benchmark (JSON)
python benchmarks/bench_e2e.py --n 1000                 # end-to-end benchmark
ruff check molcore/                                     # lint

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Documentation

• Quickstart notebook — Open in Colab
• Migrating from RDKit — API mapping for common RDKit patterns
• End-to-end GNN example — ESOL solubility benchmark
• Virtual screening pipeline

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License

MIT — see LICENSE.