bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.06.12.731585

THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication

Klamt, T.·Jaczkowski, A.·Franke, J.·Nejdl, W.
View original source ↗Export metadata ↓

Abstract

AbstractNatural products remain one of the most productive sources of pharmacologically active compounds for drug discovery. Open aggregators attribute licenses at database granularity, and the consequences of that choice have become tangible as the field grows. A recent relicensing event in one constituent source (the September 2024 transition of the Natural Products Atlas to CC BY-NC 4.0) demonstrates how database-level licensing propagates across an aggregate and motivates the per-compound audit framework presented here. The same peer cohort separately leaves classification provenance and stereoisomer-family relations coarser than either layer warrants. THEOBROMA, accessible at https://theobroma.l3s.uni-hannover.de, integrates 1,132,805 natural products from 29 open sources under a per-compound license audit that resolves each compounds license tier across all attesting sources under a most-restrictive-wins rule, identifying 900,103 compounds (79.5%) under open-use licenses and providing the per-source attestation chain and resolved tier through a dedicated audit endpoint and a query- time license filter. A three-tier classification labels all but 21 compounds by the provenance of the assignment (55.3% curated source labels, 18.2% NPClassifier tool assignments, 26.5% model-inferred). Deduplication at the full 27-character InChIKey retains 1,132,805 entries across 486,032 connectivity families, exposed via a dedicated /api/stereoisomers/ endpoint and a radial-family display. Per-compound license provenance is the primary differentiator, while classification stratification and stereoisomer-family exposure add finer-grained access to two related axes, supporting license-compatible virtual screening and isomer-specific bioactivity analysis at corpus scale. As an evolving open resource, THEOBROMA pairs continuous pipeline maintenance with interactive geographic, taxonomic, and chemical-space exploration. Graphical AbstractTHEOBROMA integrates 1,132,805 natural products from 29 open sources across three axes. A per-compound license audit resolves each compound to the most restrictive tier attested by any source, giving 891,860 permissive open, 225,536 non-commercial, 8,243 public domain and 7,166 unspecified, so that 900,103 compounds (79.5%) are open-licensed. A three-tier classification records the provenance of each label as source-supplied (55.3%), tool-assigned (18.2%), or model-inferred (26.5%), leaving 21 compounds unclassified. Deduplication at the full 27-character InChIKey retains the stereochemical and protonation variants that 14-character truncation would erase, illustrated by the (E,E)- and (Z,E)-curcumin pair shown. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/731585v2_ufig1.gif" ALT="Figure 1000"> View larger version (15K): org.highwire.dtl.DTLVardef@d5e1daorg.highwire.dtl.DTLVardef@1ded69eorg.highwire.dtl.DTLVardef@dc576corg.highwire.dtl.DTLVardef@1ef94b8_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

bioinformaticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Klamt, T., Jaczkowski, A., Franke, J., Nejdl, W.. 2026-06-16. THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication. https://doi.org/10.64898/2026.06.12.731585

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Targeted finetuning enables co-folding models to learn ligand-induced protein conformational states

Advances in protein structure prediction have enabled all-atom protein-ligand co-folding models that predict bound conformations directly from sequence and small-molecule structure. However, these models often fail to generalize to novel binding sites or alternative protein conformational states, limiting their utility for chemical biology and drug discovery. Here we show this limitation reflects training data bias rather than architectural constraints and can be overcome through targeted finetuning. Using ten previously unseen X-ray structures of Werner (WRN) helicase from a drug discovery program, we finetune Boltz-1 to learn both an allosteric binding site and a large conformational change locking the enzyme in an inactive state, while preserving accuracy on the ATP-bound state. The finetuned model generalizes to different chemical series and transfers the conformational logic across RecQ-family helicases in a binding-site sequence-dependent manner. This approach provides a blueprint for adapting foundation models as new structural and mechanistic data emerge, enabling co-folding networks to capture ligand-induced conformational switches and binding poses absent from their training data but central to biological regulation and therapeutic intervention.

bioinformatics↗
bioRxiv2026

Benchmarking single-cell foundation models for aging biology

Single cell foundation models (scFMs) provide representations of cellular states, but their utility across biological questions in aging research remains unclear. We established a benchmark of cellular representations for aging research, evaluating ten general-purpose scFMs, three aging-specific models and conventional methods across five biological questions using more than 2.5 million single cell transcriptomes. Using frozen pretrained representations, Geneformer performed best among scFMs for chronological age prediction and age pseudotime concordance, although 2,000 highly variable genes achieved higher mean performance. Several scFMs captured positive molecular age shifts across three disease contexts, consistent with reported aging-associated changes. SCimilarity performed well for rare cellular state identification across out-of-distribution datasets, exceeding aging specific models and conventional baselines. At the gene level, scGPT showed the highest recovery of reference TF target interactions, including aging-related regulatory hubs. Overall, scFMs supported diverse aging analyses, but performance depended on the biological question, highlighting their utility for rare cellular state identification and regulatory analysis.

bioinformatics↗
bioRxiv2026

CryoMV: Structure-Prior-Guided Modeling and Real-Particle Validation of Continuous Conformational Transitions in Cryo-EM

Continuous protein conformations are essential for understanding fundamental biological processes and supporting drug discovery. Although cryo-EM can resolve individual states at high resolution, recovering continuous heterogeneity from 2D particle images remains challenging. High noise, motion blur, and limited structural priors make it difficult to accurately generate and validate high-resolution continuous conformations using raw particle data. Here, we introduce cryoMV, a framework that integrates structure-prior-guided modeling with real-particle validation for continuous conformational transitions. CryoMV uses reference density maps to establish structural anchors and motion priors, models candidate transition paths between selected conformations, and transfers the learned representation to raw 2D cryo-EM particle images. Each candidate conformation is subsequently evaluated using the estimated particle poses and contrast transfer functions. Supported conformations are reconstructed through raw particle back-projection and assessed using canonical half-maps and Fourier shell correlation. On EMPIAR-10516 and EMPIAR-10345, cryoMV achieves excellent performance in terms of robustness, verifiability, and reconstruction resolution. By incorporating structure-prior modeling and evidence from the raw particles, cryoMV offers an explicit mechanism for assessing whether generated conformations are supported by experimental data and provides a practical approach to reducing model-induced artifacts in continuous cryo-EM heterogeneity analysis.

bioinformatics↗