Abstract A001: Unravelling the molecular structural and functional roles of the homologous Mouse double minute RINGs interface for targeted anticancer design
Bibliographic record
Abstract
Abstract The new yearly 1.1 million cancer surge cases and considerably increasing mortality, after two decades of decline, require urgent and effective therapy. Targeted anticancer therapy is an attractive strategy against cancer using critical receptors. Homologous Mouse Double-Minute RINGs (MDM2-MDMX) negatively regulate the p53 tumour-suppressing role by inhibiting its transcriptional activity and promoting proteasomal degradation in tumour types. Interventively, Hinokiflavone/Hinok, MMRi62, MMRi64, and MMRi71 exert a therapeutic downregulation against MDM2-MDMX by activating p53’s apoptotic arm, a mechanism that is still unclear. This study reveals the underlying dynamic conformational stabilities of the MDM2G443T-MDMX interface and its mechanistic inhibition. Integrated software visualisations/computations of the all-atoms MD simulated systems revealed relative stability (lower_RMSD_values), flexibility (higher_RMSF_values), and highly inter-residual displacement among unbound and inhibitor-bound systems. The ligand-bound MDM2G443T-MDMX showed remarkable secondary structure transitions. MMGB(PB)SA binding free energies (-22.69, -26.42, -20.30 kcal/mol) revealed promising inhibitors’-MDM2G443T-MDMX interactions. ARG13, PRO45, LYS42, and PRO14 have the highest binding energy contributions to the RINGs. Hinok showed dual interactions with MDM2G443T-MDMX RINGs over 200 ns, indicating dual potential inhibition compared to the interactions of the MMRis with MDM2 only. These findings provide deep molecular insights into the MDM2G443T-MDMX RINGs conformation and can be extrapolated to inhibitors' downregulatory induction for future potential anticancer development. Citation Format: Adeniyi Thompson Adewumi, Salerwe Mosebi. Unravelling the molecular structural and functional roles of the homologous Mouse double minute RINGs interface for targeted anticancer design [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr A001.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.013 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".