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This is a Track Two entry from Taipei Medical University. Faculty and students from the College of Interdisciplinary Studies and the College of Pharmacy.

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The gene is BUB1B. The protein is BubR1. The allele is asparagine one thousand two, to lysine.

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This child is compound heterozygous: one truncating allele, and missense N1002K on helix alpha G. That is the same helix as the known mosaic variegated aneuploidy hotspot, L1012P. Kinase-domain missense alleles in this disease do not kill catalytic chemistry.

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They make BubR1 unstable. Lysine one thousand two is a new, solvent-exposed primary amine. Wild-type asparagine cannot be ubiquitylated there. Lysine can.

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We first asked whether an approved drug could pull the mutant C-lobe back toward wild type. Three thousand six hundred nineteen FDA and pharmacopeial compounds went through DynamicBind. The empty mutant already scored forty-nine point nine against wild type.

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No ligand beat that. The best similarity was forty-seven. Poses drifted twenty-five to thirty-two angstroms from the lysine. Structure reversal failed.

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We re-scored the same FDA poses for contact to the new amine. Aprepitant won on pocket occupancy, but it failed the hydrogen-bond gate.

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The approved shortlist that survived is bicalutamide, hederagenin, glimepiride, infigratinib, and cynarin. A local generator never beat those seeds.

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We then opened a larger catalog. Two million four hundred twenty-seven thousand blood-brain-barrier filtered ligands, docked in a twenty-two angstrom box on mutant lysine one thousand two. Ten poses remain.

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Rank ten is notoamide B, a fungal natural product in an anticancer alkaloid family. It is not an F.D.A. drug. These ten ranks are Vina plus geometry, not induced-fit confirmation.

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In parallel we knocked down BUB1B with shRNA in HeLa. Nuclei drop by half. Micronuclei and pyknosis rise.

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That nuclear change is the screening assay. A hit is a drug that reverses the phenotype. It does not have to bind BubR1.

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If this work is awarded, the money does not buy more G.P.U.s. It funds a real F.D.A.-approved-drug screen on that knockdown, run with the Academia Sinica high-throughput screening core. Computational docking gave us a mechanism story.

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The prize is for phenotype reversal in cells, with drugs that can already be used in people. That is testable. It is not a treatment yet.