{
  "abstract": "Topological and quantum-inspired molecular representations are increasingly proposed for drug discovery, but their predictive value relative to classical fingerprints on naturalproduct chemical space remains unclear.We benchmark a persistent-homology Topological Fingerprint (TFP), a Tucker-compressed Tensor Network Embedding (TNE), and simulated Quantum Kernel Scores (QKS) against classical baselines on 19 849 computationally generated candidates inspired by African natural-product antimalarials, with computationally predicted activity labels.Persistent homology decomposes the scaffold paradox into conserved H 1 ring features and divergent H 0 connectivity: 92.6 % of expanded molecules are whole-molecule Tanimoto-distinct from seeds while 69.3 % retain seed scaffolds.TNE compresses molecular tensors to 192 elements at 6.1× real-atom compression (reconstruction error 0.113) and retains docking-score-predictive information, competitively on PfDHFR (R 2 = 0.473 versus 0.461 for ECFP4) though below ECFP4 on PfATP4 and PfCRT.For activity prediction (n = 19 836, 5-fold cross-validation), ECFP4 achieves AUC 0.948 under random splitting and 0.822 when folds are grouped by Bemis-Murcko scaffold, the panel spanning only 632 scaffolds; the hybrid (TFP+TNE+QK) reaches 0.888, with QKS the principal contributor within that hybrid (∆ = -0.040),which nonetheless remains below ECFP4.Stacking TFP and TNE onto ECFP4 changed AUC by -0.000 2 (p = 0.084).The quantum kernel was not detectably different from a tuned RBF internally (p = 0.060) and performed lower on the ChEMBL label-source-shift panel (AUC 0.817 versus 0.847; p = 0.021).These representations add diagnostic and interpretive information under the tested protocols, but not predictive performance beyond ECFP4.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physics, Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon",
    "Department of Medical Imaging and Radiation Sciences",
    "Université de Sherbrooke",
    "Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Myke Vital Sao Temgoua",
      "orcid": "0009-0004-5170-2309"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Pierre TCHAPET NJAFA",
      "orcid": "0000-0002-1936-8353"
    },
    {
      "affs": [
        0
      ],
      "name": "Serge Guy Nana Engo",
      "orcid": "0000-0002-7484-3508"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Penabei Samafou",
      "orcid": "0000-0002-9683-7678"
    },
    {
      "affs": [
        3
      ],
      "name": "Wilfred Fon Mbacham"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b67r3fgqb8tbv.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15007167/v2",
  "fulltext_url": null,
  "id": "b67r3fgqb8tbv",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15007167/v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7213956199",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15007167/v2",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-20",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/b67r3fgqb8tbv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15007167",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15007167/v2"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Do topological and quantum-inspired molecularrepresentations add value? Evidence from Africannatural-product-inspired antimalarial chemical space",
  "title_text": "Do topological and quantum-inspired molecularrepresentations add value? Evidence from Africannatural-product-inspired antimalarial chemical space",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/b67r3fgqb8tbv",
  "venue": "ChemRxiv",
  "versions": []
}