Quantum Bio Scout — Prospective prediction lock of 3 novel small-molecule leads (BIO_07a, BIO_28a, BIO_54a) for CHEMONE wet-lab validation, June 2026 (v4, assay protocol corrected)

Quantum Bio Scout is a solo-developed end-to-end in-silico drug discoveryarchitecture built over 6 months by a single architect. This Zenodo recordpublishes the prospective prediction lock (v4) for 3 novel small-moleculelead compounds, deposited BEFORE wet-lab synthesis and IC50 measurement byCHEMONE Co., Ltd. (Korea). All predictions are locked here so that anypost-measurement comparison is unambiguously prospective. v4 supersedes v3 (DOI: 10.5281/zenodo.20116561). v4 updates ONLY the wet-labassay protocol fields (readout, dose points, dose range, replicates) to matchthe CHEMONE 2026-05-07 standard service inquiry document. Predicted IC50values, target cell lines, compound identities (SMILES, InChIKey), and allhypotheses remain identical to v3 — preserving anti-retrofit integrity. ═══════════════════════════════════════════════════════════════════════BACKGROUND═══════════════════════════════════════════════════════════════════════ Industry baseline for drug discovery: • Big Pharma: 100-500 person teams • AI drug-discovery startups: 30-100 person teams • This system: 1 person The architecture tests whether a single individual can close thein-silico → wet-lab loop (planning → generation → validation → handoff)as an end-to-end system. Capabilities: • Antibody-drug conjugate (ADC) design — HER2-trastuzumab (PDB 1N8Z) interface analysis via quantum simulators (Quandela photonic + Pasqal Rydberg + Qrunch VQE); extensible to other antibodies. • Small-molecule de novo generation — bioisostere SMARTS (Patani 1996), MoLeR scaffold-decoration, BRICS combinatorial. • Peptide design — ESM-2 (Meta AI) anchor-seeded sampling. • IC50 simulation — AutoDock Vina 1.2.7 + Boltz-2 v2.2.1 (CPU). • ADMET safety — TDC ML + RDKit + SIDER 4.1 + LINCS L1000. 43 tools, 83 SQLite tables, Layer 1/2/3 separation (compute /interpretation / report). LLM (Mistral Large 3) never generatesnumerical values — all numbers come from Layer 1 deterministiccomputation. ═══════════════════════════════════════════════════════════════════════3 LOCKED COMPOUNDS (2026-05-11, predictions unchanged in v4)═══════════════════════════════════════════════════════════════════════ All three are novel structures (zero PubChem Tanimoto > 0.85 hits)generated via bioisosteric transforms of expired-patent parent drugs. Compound 1 — BIO_07a (Vorinostat variant) Parent: Vorinostat (DRG_040) Transform: amide → urea Target: HDAC1 (UniProt Q13547) SMILES: O=C(CCCCCCCNC(=O)Nc1ccccc1)NO Properties: MW 293.37, logP 2.65, QED 0.32, rotbonds 9 Vina ΔG: -6.11 kcal/mol (Δ vs parent: -0.30) Boltz-2 predicted IC50: 27.4 nM ADMET: bioavailability F 0.745, hERG risk 0.18 (low) Novelty: 0 PubChem near-analogs Compound 2 — BIO_28a (Niclosamide variant) Parent: Niclosamide (DRG_115) Transform: NO2 → CONH2 (carbamoyl) Target: β-catenin / Wnt pathway (UniProt P35222) SMILES: NC(=O)c1ccc(NC(=O)c2cc(Cl)ccc2O)c(Cl)c1 Properties: MW 325.15, logP 3.05, QED 0.81, rotbonds 3 Vina ΔG: -7.37 kcal/mol (Δ vs parent: -0.22) Quality gate: PASS ADMET: bioavailability F 0.89 (highest), hERG risk 0.27 (low) Novelty: 0 PubChem near-analogs Compound 3 — BIO_54a (Mesalamine variant) Parent: Mesalamine (DRG_248) Transform: COOH → CH2-B(OH)2 (boronic acid) Target: β-catenin / Wnt pathway (UniProt P35222) SMILES: Nc1ccc(O)c(CB(O)O)c1 Properties: MW 166.97, logP -0.47, QED 0.27, rotbonds 2 Vina ΔG: -6.59 kcal/mol (Δ vs parent: -2.25, ~50-fold predicted improvement) ADMET: bioavailability F 0.705, hERG risk 0.31 (low) Novelty: 0 PubChem near-analogs ═══════════════════════════════════════════════════════════════════════BOLTZ-2 CALIBRATION BASELINE (PRE-VALIDATED)═══════════════════════════════════════════════════════════════════════ Vorinostat parent (HDAC1): Boltz-2 predicted IC50: 25.48 nM Literature IC50 range: 50-150 nM (median ~85 nM) Log10 error: 0.523 Verdict: within 0.5 log10 — calibration layer validated. ═══════════════════════════════════════════════════════════════════════ANTI-RETROFIT INTEGRITY═══════════════════════════════════════════════════════════════════════ SHA-256 self-hash of prediction_lock_v4.json: 1b149d62ec02e6ef1e9ec87955dba74d593c637afee081c5bc09b365fca3fbdf (File-level SHA-256 of final lock file, including sha256_self field: 231b5adbb5f3844aa151f5e6897ae852fc53ca3801d3541e6891d6a5624c0d19) v3 SHA-256 (preserved at DOI 10.5281/zenodo.20116561): c785152a34e069492d847b0afc788dada8946a25c4f5cc683b05496144fef7ff This record was deposited BEFORE CHEMONE wet-lab measurement.Any post-measurement modification of analog SMILES, predicted ΔG/IC50,or hypotheses would be immediately detectable via DOI-versionedimmutability and SHA-256 file integrity. ═══════════════════════════════════════════════════════════════════════WET-LAB MEASUREMENT PLAN (June 2026) — v4 update═══════════════════════════════════════════════════════════════════════ Partner: CHEMONE Co., Ltd. (Korea, R&D Director Yang Jin)Assay: CCK-8 (450 nm readout), 72h exposureDose-response: 0.1 / 1 / 10 / 100 / 1,000 μM (5-point)Replicates: n=3 triplicate Cell lines and benchmarks (unchanged from v3): • BIO_07a → MCF-7 or HCT-116, benchmark Vorinostat (parent) • BIO_28a → HCT-116, benchmark Niclosamide (parent) • BIO_54a → Caco-2 or HT-29, benchmark Mesalamine (parent) QC: HPLC purity ≥ 95% + LC-MS m/z confirmation + 1H NMR. Results will be deposited as a linked Zenodo record upon completion. ═══════════════════════════════════════════════════════════════════════HYPOTHESES UNDER TEST (unchanged from v3)═══════════════════════════════════════════════════════════════════════ H1. A solo architect can run end-to-end in-silico drug discovery (planning → generation → validation → wet-lab handoff). H2. BIO_* novel bioisostere variants show comparable or improved cell-line IC50 versus their expired-patent parents. H3. Boltz-2 predicted IC50 matches wet-lab measurement within ±0.5-1.0 log10 (Vorinostat parent already validated within 0.5 log). ═══════════════════════════════════════════════════════════════════════FILES IN THIS RECORD (v4)═══════════════════════════════════════════════════════════════════════ • prediction_lock_v4.json — canonical machine-readable lock • prediction_lock_v4_summary.md — human-readable summary with tables • announcement_kr.md — public announcement (Korean) • announcement_en.md — public announcement (English) • sha256_checksums.txt — file integrity verification • README.md — Zenodo record metadata + upload procedure License: Creative Commons Attribution 4.0 International (CC-BY 4.0).Architecture code repository: forthcoming on GitHub (MIT license). ═══════════════════════════════════════════════════════════════════════CITATION═══════════════════════════════════════════════════════════════════════ [Sungil Oh]. (2026). Quantum Bio Scout — Prospective prediction lockof 3 novel small-molecule leads (BIO_07a, BIO_28a, BIO_54a) forCHEMONE wet-lab validation, June 2026 (v4, assay protocol corrected).Zenodo. https://doi.org/10.5281/zenodo.20152623 v3 reference (preserved):[Sungil Oh]. (2026). Quantum Bio Scout — Prospective prediction lockof 3 novel small-molecule leads (BIO_07a, BIO_28a, BIO_54a) forCHEMONE wet-lab validation, June 2026 (v3).Zenodo. https://doi.org/10.5281/zenodo.20116561