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Record W4385835161 · doi:10.1021/jacs.3c04045

Programing Chemical Communication: Allostery vs Multivalent Mechanism

2023· article· en· W4385835161 on OpenAlexafffund
Dominic Lauzon, Alexis Vallée‐Bélisle

Bibliographic record

VenueJournal of the American Chemical Society · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced biosensing and bioanalysis techniques
Canadian institutionsUniversité de Montréal
FundersNatural Sciences and Engineering Research Council of CanadaCanada Research Chairs
KeywordsAllosteric regulationChemistryMolecular switchActivator (genetics)Synthetic biologyChemical biologyNanotechnologyMechanism (biology)Molecular machineDNABiophysicsComputational biologyBiological systemMoleculeBiochemistryEnzymeReceptor

Abstract

fetched live from OpenAlex

The emergence of life has relied on chemical communication and the ability to integrate multiple chemical inputs into a specific output. Two mechanisms are typically employed by nature to do so: allostery and multivalent activation. Although a better understanding of allostery has recently provided a variety of strategies to optimize the binding affinity, sensitivity, and specificity of molecular switches, mechanisms relying on multivalent activation remain poorly understood. As a proof of concept to compare the thermodynamic basis and design principles of both mechanisms, we have engineered a highly programmable DNA-based switch that can be triggered by either a multivalent or an allosteric DNA activator. By precisely designing the binding interface of the multivalent activator, we show that the affinity, dynamic range, and activated half-life of the molecular switch can be programed with even more versatility than when using an allosteric activator. The simplicity by which the activation properties of molecular switches can be rationally tuned using multivalent assembly suggests that it may find many applications in biosensing, drug delivery, synthetic biology, and molecular computation fields, where precise control over the transduction of binding events into a specific output is key.

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.012
GPT teacher head0.290
Teacher spread0.278 · 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 designTheoretical or conceptual
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

Citations26
Published2023
Admission routes2
Has abstractyes

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Same venueJournal of the American Chemical SocietySame topicAdvanced biosensing and bioanalysis techniquesFrench-language works237,207