COSMolKit — Rust-native cheminformatics toolkit

COSMolKit is a Rust-native cheminformatics and structural biology toolkit with first-class Python bindings. It provides molecular graph operations, SMILES/SMARTS and molecular file workflows, 2D depiction, native 3D conformer generation, UFF/MMFF optimization, fingerprints, molecular descriptors, InChI, batch processing, and protein structure APIs. Selected workflows are also available directly in the browser through the COSMolKit Web Tools.

For supported cheminformatics operations, RDKit-compatible behavior is treated as the correctness floor. COSMolKit uses boundary-scoped parity claims: a feature is considered parity-covered only when its documented reference surface passes the required exact or numerical comparisons. Fixed reference oracles, source-backed implementations where reference semantics require them, committed regression corpora, and explicit capability boundaries are used together; aggregate success rates or approximate similarity are not treated as substitutes for behavioral parity.

COSMolKit combines a native Rust API with Python interfaces designed for array-oriented scientific and machine-learning workflows. Molecular graphs, coordinates, fingerprints, bounds matrices, and structural data are exposed in forms suitable for NumPy, PyTorch, dataset processing, and model-building pipelines.

Documentation

• Python documentation: https://kit.cosmol.org/
• Interactive Web Tools: https://tools.cosmol.org/tools
• Rust crate notes: crates/cosmolkit/README.md
• Feature parity scope: dev/parity_scope.md

Validation Status

COSMolKit treats parity as source-backed semantic equivalence within explicitly documented boundaries, not as statistical agreement of final outputs. Compatibility-critical chemistry is implemented as a line-by-line, source-backed port with explicit operation contracts and traceable correspondence to pinned upstream code. Validation corpora verify that port; they are not used to iteratively tune heuristic reimplementations until outputs happen to agree.

The comparison boundary therefore extends well beyond final strings. Covered surfaces compare exact bytes, bits, return status, complete atom and bond state, stereochemistry, derived state and invariants, RNG state, seed handling, and random draw sequences where stochastic behavior is part of the contract, every matrix entry, coordinates, energies, and every gradient component where applicable. Discrete results must match exactly; declared numerical tolerances reach 1e-8 for matrix entries and 1e-6 for coordinates, energies, and gradients. 99% or 99.9% agreement remains unfinished when any covered mismatch exists.

This boundary is stress-tested against a complete ChEMBL 37 profile: 2,897,819 source records, 2,897,804 of them mutually parseable, across 22 sharded test phases against pinned RDKit 2026.03.1. The profile performs billions of comparisons, expands parameter spaces into matrices of up to 768 branches, repeats complete matrices to expose instability, permutes operation order, and checks scalar, one-thread, multi-thread, batch, and shared-object concurrent paths.

Every discovered mismatch is traced back to the corresponding upstream logic, corrected at the source-port level, and permanently retained as a focused regression rather than hidden by corpus-specific adjustments. This discipline limits semantic debt by preventing convenient local fixes from accumulating into undocumented chemistry behavior.

The parity suite uses three complementary validation layers. The complete ChEMBL 37 profile provides large-scale stress coverage; the maintained 5,000-record corpus runs exhaustive parameter matrices not yet practical across the full ChEMBL profile; and the 152-record project corpus keeps focused regressions fast enough for daily testing.

See dev/parity_scope.md for exact corpus eligibility, comparison counts, tolerances, per-feature boundaries, retained-case replays, and upstream surfaces outside the current claim.

Installation

pip install cosmolkit

Core Concepts

• Value-style molecules: methods such as with_hydrogens(), without_hydrogens(), with_kekulized_bonds(), and with_2d_coordinates() return new molecule values, keeping topology-changing operations explicit and preventing derived chemistry state from being silently invalidated.
• Explicit mutation: in-place Molecule operations always end with _. The trailing underscore has no other public Molecule meaning.
• Explicit errors: invalid input and unsupported behavior are surfaced as errors instead of silent fallbacks.
• Batch-native processing: MoleculeBatch keeps input order, supports structured per-record failures, and can run batch transforms and exports with configurable parallelism.
• Array-friendly data access: coordinates, bounds matrices, fingerprints, and graph features are exposed in forms that fit Python numerical workflows.
• Source-backed 3D workflows: conformer generation and UFF/MMFF optimization are available through the public Python API, and atom chiral tags can be assigned from a selected 3D conformer with pinned-RDKit parity.

Value-Style Transformations

Normal molecule operations return new objects and do not mutate their inputs. This follows the same explicit-dataflow direction as modern dataframe libraries: users can reason about each transformation as a new value while COSMolKit can share unchanged internal storage efficiently.

from cosmolkit import Molecule

mol = Molecule.from_smiles("CCO")
mol_h = mol.with_hydrogens()

assert mol is not mol_h

Python Quick Start

from cosmolkit import Molecule, MoleculeBatch

mol = Molecule.from_smiles("c1ccccc1O")
mol_2d = mol.with_2d_coordinates()

print(mol_2d.to_smiles())
print(mol_2d.coordinates_2d())

mol_3d = mol.with_hydrogens().with_3d_conformer()
print(mol_3d.coordinates_3d().shape)

svg = mol_2d.to_svg(width=400, height=300)
mol_2d.write_png("phenol.png", width=400, height=300)

fp = mol.fingerprint_morgan(radius=2, n_bits=2048)
print(fp.on_bits())

batch = (
    MoleculeBatch.from_smiles_list(
        ["CCO", "c1ccccc1", "CC(=O)O"],
        sanitize=True,
        errors="keep",
    )
    .with_parallel_jobs(8)
    .with_progress_bar(False)
)

prepared = batch.with_hydrogens(errors="keep").with_2d_coordinates(errors="keep")
print(prepared.valid_mask())
print(prepared.to_smiles_list())

prepared.to_images(
    "molecule_images",
    format="png",
    size=(300, 300),
    errors="keep",
    filenames=["ethanol", "benzene", "acetate"],
)

Protein Structures

Use Protein when the workflow is focused on protein chains rather than the full structural table.

from cosmolkit import Protein

protein = Protein.from_pdb("1crn.pdb")

print(protein.num_chains())
print(protein.num_residues())
print(protein.num_atoms())

for chain in protein.chains():
    print(chain.index(), chain.kind(), len(chain))
    for residue in chain.residues():
        print(residue.name(), residue.kind(), len(residue))

SDF and Dataset Workflows

SdfDataset builds a lightweight index of SDF record byte ranges, so individual records and chunks can be read without loading an entire file into memory. Molfile-only readers such as Molecule.read_mol() follow RDKit MolFromMolBlock boundaries: they stop after the first M END line and leave trailing SDF data fields to the SDF APIs.

from cosmolkit import SdfDataset

dataset = SdfDataset.open("library.sdf")
print(len(dataset))

record = dataset[0]
mol = record.molecule()

for batch in dataset.batches(size=1024, errors="keep", n_jobs=8):
    smiles = batch.to_smiles_list()

Conformer Generation And Optimization

from cosmolkit import EmbedParameters, Molecule

mol = Molecule.from_smiles("CC(=O)NC").with_hydrogens()

params = EmbedParameters.etkdg_v3()
params.random_seed = 0xF00D
params.num_threads = 1
params.track_failures = True

embedded = mol.with_3d_conformer(params)
print(embedded.num_conformers())
print(embedded.coordinates_3d().shape)
print(params.failures)

multi = mol.with_3d_conformers(5, params)
print(multi.num_conformers())

if embedded.has_uff_params():
    uff = embedded.with_uff_optimized(max_iters=200)
    print(uff.energy())

if embedded.has_mmff_params():
    mmff = embedded.with_mmff_optimized(max_iters=200)
    print(mmff.needs_more())

with_3d_conformer() follows RDKit's ETKDG behavior for trusted molecular graphs: molecules without explicit hydrogens are embedded as heavy-atom-only conformers instead of failing or automatically adding hydrogens. Calling with_hydrogens() first is recommended for all-atom geometry, force-field optimization, and hydrogen-bond-sensitive workflows. Coordinate-only inputs such as XYZ blocks do not contain a bond topology and are not valid ETKDG inputs until a trusted graph has been constructed.

Feature Areas

• Molecular graph construction and inspection
• SMILES parsing and writing
• MOL/SDF reading and writing
• MOL2 reading with RDKit-style Mol2ParserParams
• XYZ block reading
• Four scalar InChI APIs with exact source-defined official-C/RDKit parity and structured errors
• Stable 3D atom-chiral-tag assignment with exact pinned-RDKit full-state parity
• Hydrogen transforms and Kekulization
• Sanitization and chemistry problem detection
• 2D coordinate generation and SVG/PNG depiction
• Native 3D conformer generation with DG/KDG/ETDG/ETKDG parameter presets
• UFF/MMFF optimization of generated or imported 3D conformers
• Morgan, MACCS, RDKit topological, and Avalon fingerprints for the validated exact-parity branches
• Distance-geometry bounds matrices
• Substructure matching and SMARTS parse metadata
• Ordered batch transforms and exports
• Python pickle round-tripping for Molecule
• PDB/mmCIF molecule-block parsing and protein projection APIs
• Support-status metadata for public features

Design Principles

COSMolKit aims to be Python-friendly, batch-friendly, and suitable for model-building workflows.

• Correctness comes before breadth.
• Public transforms use value semantics.
• Mutation-capable workflows are explicit.
• Fail-closed capability boundaries: a separately named capability outside documented support returns a structured error rather than fabricated chemistry. This is an API design rule, not an accepted mismatch within a supported feature.
• RDKit-parity behavior is the correctness floor for supported cheminformatics features.
• High-throughput APIs should preserve input order and expose per-record failures.
• Reference semantics come before heuristic approximation; semantic debt is treated as a correctness risk.

Examples

Python examples live in python/examples/. For the current InChI interface, see python/examples/inchi_roundtrip.py.

Development

Small focused Rust test filters may use the default debug profile while iterating:

cargo test -p cosmolkit-core --features op-contracts-strict <test-filter>

Large local runs, parity suites, and CI tests should use release mode with the same strict feature set:

cargo test -p cosmolkit-core --release --features op-contracts-strict

Release-mode testing keeps operation contracts and runtime invariants enabled through op-contracts-strict; optimized release builds for distribution use default features unless explicit runtime checks are requested.

Roadmap

Status labels:

• ✅ stable public functionality within its documented supported scope
• 🧪 public experimental feature; available, but its behavior or API may change
• 🚧 planned or not yet public

The ✅ status applies to the documented COSMolKit scope. It does not claim that every API or input branch from an upstream reference library is implemented; separately named upstream capabilities outside that scope are not represented as implemented. Every path inside a parity-covered boundary is still required to match; individual failing rows cannot be reclassified as out of scope.

Chemistry Core

Goal: keep the supported molecular core correct before expanding breadth.

• ✅ Molecule, atom, and bond graph model
• ✅ SMILES parsing
• ✅ SMILES writing with RDKit-style writer options for supported branches
• ✅ Ring perception, valence handling, aromaticity, and Kekulization
• ✅ Hydrogen addition and removal
• ✅ Sanitization for supported chemistry workflows
• ✅ Stereochemistry inspection for supported atom and bond states
• ✅ Atom chiral-tag assignment from selected 3D conformers, with exact pinned-RDKit assignChiralTypesFrom3D parity across 77 fixed full-state oracle records
• ✅ Distance-geometry bounds matrices
• ✅ Native 3D conformer generation and UFF/MMFF post-optimization for supported molecules
• ✅ Molecule.to_inchi(), Molecule.to_inchi_key(), inchi_to_key(), and Molecule.from_inchi() for source-defined behavior; official-C undefined allocation behavior returns a structured error
• ✅ Morgan fingerprints and Tanimoto similarity for the validated exact-parity branches
• ✅ MACCS fingerprints for the validated exact raw/public projection
• ✅ Source-backed RDKFingerprint/topological and Avalon fingerprints with zero-mismatch ChEMBL 37 validation across 2,897,804 mutually parseable molecules and 113,014,356 exact profile comparisons, including complete topological atomBits/bitInfo provenance
• ✅ Substructure matching and Python SMARTS parse metadata
• ✅ Molecular descriptors: average/exact molecular weight, formula, H-bond donor/acceptor counts, fraction Csp3, Crippen logP/MR, TPSA, aromatic-ring count, rotatable-bond modes, and QED for the documented parameter space

File I/O and Depiction

Goal: make common molecule import, export, and visualization workflows usable from Python.

• ✅ MOL/SDF reading
• ✅ MOL2 reading
• ✅ XYZ block reading
• ✅ SDF dataset indexing for large files
• ✅ SDF writing for supported V2000/V3000 branches
• ✅ PDB block to molecule conversion
• ✅ mmCIF block to molecule conversion through the same molecule-conversion profile
• ✅ 2D coordinate generation
• ✅ SVG drawing
• ✅ PNG export
• ✅ RDKit-style visual parity testing for supported depiction output
• 🚧 Annotation overlays and richer drawing customization
• ✅ 3D conformer generation and embedding APIs

Batch-Native Workflows

Goal: make high-throughput molecule preparation and export a core product identity.

• ✅ Ordered MoleculeBatch.from_smiles_list()
• ✅ Batch transforms for sanitization, hydrogens, Kekulization, and 2D coordinates
• ✅ Configurable parallelism with with_parallel_jobs()
• ✅ Configurable progress display with with_progress_bar()
• ✅ Per-record errors, valid masks, and error reports
• ✅ Batch SMILES, image, and SDF export paths
• ✅ Golden parity tests for parallel batch behavior
• 🚧 More streaming and chunked dataset workflows

Protein and Structural Biology

Goal: provide practical Biopython-like structure workflows without forcing users through low-level structural tables.

• ✅ Protein.from_pdb() / Protein.from_mmcif() high-level entry points
• ✅ Protein chain, residue, and atom iteration
• ✅ Protein-only projection from broader structural data
• ✅ PDB/mmCIF structural parsing
• 🚧 Selection utilities for chains, residues, atoms, and neighborhoods
• 🚧 Ligand, nucleic-acid, and mixed-structure ergonomic APIs

Python API and ML Readiness

Goal: expose verified molecular behavior through a practical Python interface.

• ✅ Stable value-style mutation contract for public molecule transformations
• ✅ Graph, coordinate, fingerprint, descriptor, and bounds-matrix accessors
• ✅ Python examples for drawing, SDF-to-SMILES, pickle round-tripping, batch processing, and proteins
• ✅ Type stubs and documentation coverage
• 🚧 Stable model-ready graph exports
• 🚧 NumPy / PyTorch oriented adapters
• 🚧 Molecular tokenization and AI-native geometry helpers

Browser and Deployment

Goal: make validated COSMolKit functionality usable without requiring a local Python or Rust installation.

• ✅ COSMolKit Web Tools for browser-based molecular workflows
• ✅ Browser-native deployment of selected COSMolKit functionality through WebAssembly
• 🚧 Broader JavaScript bindings
• 🚧 Expansion of browser-native chemistry and structural-biology workflows

Respect for RDKit

COSMolKit is developed with deep respect for RDKit and the broader open-source cheminformatics community. The goal is a Rust-native implementation that preserves interoperability and faithfully ports reference behavior where appropriate, while offering a deterministic Python API and AI-native extension surface.

License

COSMolKit is licensed under the MIT License. Vendored sources and externally derived test fixtures retain their upstream copyright and license terms as documented beside those files.