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Record W1995671471 · doi:10.1039/c1ib00053e

Limitations of conventional inhibitor classifications

2011· article· en· W1995671471 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
aboutThe title or abstract carries a Canadian signal from the geographic lexicon.

Bibliographic record

VenueIntegrative Biology · 2011
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsDalhousie UniversityMount Saint Vincent UniversityCarleton University
Fundersnot available
KeywordsNova scotiaSAINTLibrary scienceClassicsMedicineArt historyHistoryComputer scienceArchaeology

Abstract

fetched live from OpenAlex

Enzyme inhibitors are usually classified as competitive, non-competitive or mixed non-competitive. Each of these designations has a serious limitation in that it only describes an extreme of inhibitory behaviour. The non-competitive inhibition equation only considers an approach to complete inhibition of the catalytic turnover rate, while the competitive inhibition equation predicts an infinite increase in the Michaelis-Menten constant (decrease in enzyme affinity for substrate), resulting from increased inhibitor concentration. Both of these models exclude the possibility of a finite inhibitor-induced change in the kinetic parameters of the enzyme they are affecting. They also exclude the possibility of an inhibitor affecting both the substrate affinity and the catalytic turnover at the same time. Mixed non-competitive inhibition describes a hybrid form of inhibition displaying some characteristics of both competitive and non-competitive inhibition. It also suffers from an inability to describe finite changes in activity and to describe concomitant changes in substrate affinity and catalytic turnover. Two inhibitor binding constants are invoked in this equation, suggesting that such inhibitors interact with the enzyme in two completely independent manners. From these considerations, it is suggested here that conventional equations do not adequately describe observed kinetic data due to a lack of distinction between the mass action binding term describing inhibitor-enzyme association and the terms representing the actual effect of the inhibitor on the enzyme. Herein we describe an alternate approach for representing enzyme activity modulation based on a re-examination of conventional inhibition equations. The arguments presented are illustrated using the known competitive inhibition of Kallikrein with benzamidine.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: Theoretical or conceptual
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.742
Threshold uncertainty score0.275

Codex and Gemma teacher scores by category

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

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 head0.251
GPT teacher head0.349
Teacher spread0.098 · 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