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Record W4414162235 · doi:10.1021/jacs.5c09166

A Complete Mechanistic Framework for Molecular Glue Characterization

2025· article· en· W4414162235 on OpenAlexaff
Maxime Couturier, Ryan Guilbert, Paul Clarkson, Argyrides Argyrou

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsDiscovery Centre
FundersAstraZenecaAstraZeneca UK
KeywordsCooperativityCharacterization (materials science)Förster resonance energy transferMolecular modelMolecular bindingMoleculeFluorescenceMolecular dynamics

Abstract

fetched live from OpenAlex

The use of molecular glues to modulate protein-protein interactions has emerged as a promising approach to drug previously intractable targets. Despite strong interest in this modality, a comprehensive theoretical framework is lacking. We have established a complete mechanistic analysis which enables the determination of molecular glues' binding and cooperativity values from a simple biochemical matrix experiment. We validated the model using numerical integration and experimental data from fluorescence resonance energy transfer and fluorescence polarization assays. As the derived models enable the determination of all thermodynamic parameters of any molecular glue, they have significant applications in drug discovery, particularly for molecular glue optimization and characterization of neo-substrates.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.003
Scholarly communication0.0020.004
Open science0.0030.002
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0040.001

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.

Opus teacher head0.007
GPT teacher head0.263
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2025
Admission routes1
Has abstractyes

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Same venueJournal of the American Chemical SocietySame topicProtein Degradation and InhibitorsFrench-language works237,207