“Smac”ing the Life out of XIAP
Bibliographic record
Abstract
X‐linked inhibitor of apoptosis protein (XIAP) is a key prosurvival protein that blocks apoptosis by inhibiting both the intrinsic and extrinsic pathways. Released by the mitochondria when under stress, XIAP is a homodimer, with 2 sets of repeating type I and type II baculoviral IAP domains: BIR1, BIR2 and BIR3, and RING. XIAP has a capacity to block apoptosis by directly inhibiting caspases 3,7 and 9. Second mitochondria‐derived activator of caspases (Smac) is a 184 amino acid chain. Smac antagonizes XIAP by attaching to the BIR3 domain inhibiting the binding of caspase‐9. Synthetic Smac mimetics (SMs) have been designed to duplicate the N‐terminal tetrapeptide (AVPI) or the IAP‐binding motif (IBM). Our model aims to show two BIR3 domain of a homodimer XIAP, bound to the IAP‐binding motif (IBM) of a Smac dimer. Selective antagonism of XIAP, specifically the BIR3 by Smac/SMs or monotherapy is not enough to kill cancer cells, however, it could be combined with immunotherapy, specifically virotherapy. This tricks the immune system to think that the cancer cells have a virus, which stimulates the immune antiviral response and creates an overproduction of immune cells known as a “cytokine storm”, to kill cancer cells. Support or Funding Information The Ashbury College MSOE Center for BioMolecular Modeling SMART Team used 3D modeling and printing technology to examine structure‐function relationships between Smac and BIR3 of XIAP.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.013 | 0.003 |
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".