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Record W4394569006 · doi:10.26434/chemrxiv-2024-v10t8

ABC of Kd Accuracy

2024· preprint· en· W4394569006 on OpenAlexaff
Tong Ye Wang, Jean‐Luc Rukundo, Zhiyuan Mao, Sergey N. Krylov

Bibliographic record

VenueChemRxiv · 2024
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsYork University
Fundersnot available
KeywordsSystematic errorLimitingDissociation (chemistry)ChemistryAccuracy and precisionRegressionLinear regressionStatisticsComputer scienceEconometricsMathematicsEngineering

Abstract

fetched live from OpenAlex

The equilibrium dissociation constant (Kd) is a major characteristic of affinity complexes and one of the most frequently determined physicochemical parameters. Despite its significance, the values of Kd obtained for the same complex under similar conditions often exhibit considerable discrepancies and sometimes vary by orders of magnitude. These inconsistencies highlight the susceptibility of Kd determination to large systematic errors, ultimately leading to misconceptions and significant misallocation of research and development resources. It is imperative to both minimize and quantitatively assess the systematic errors inherent in Kd determination. Traditionally, Kd values are determined through nonlinear regression of binding isotherms. This analysis utilizes three variables: concentrations of two reactants and a fraction R of unbound limiting reactant. The systematic errors in Kd arise directly from systematic errors in these variables. In this study, we thoroughly analyze the sources of systematic errors within these variables, aiming to mitigate their impact on Kd accuracy. Through this analysis, we illustrate how each source contributes to inaccuracies in Kd determination. Additionally, we propose a method for quantitatively assessing the confidence interval of systematic errors in concentrations, a crucial step towards quantitatively evaluating Kd accuracy. While presenting original findings, this paper also reiterates the fundamentals of Kd determination, hence, guiding researchers across all proficiency levels. By shedding light on the sources of systematic errors and offering strategies for their mitigation, our work will help researchers to enhance the accuracy of Kd determination thereby making binding studies more reliable.

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)0.036
metaresearch head score (Gemma)0.232
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.036
Threshold uncertainty score0.190

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0360.232
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0050.004
Science and technology studies0.0020.003
Scholarly communication0.0090.006
Open science0.0050.006
Research integrity0.0030.005
Insufficient payload (model declined to judge)0.0070.005

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 head0.043
GPT teacher head0.349
Teacher spread0.306 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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

Citations1
Published2024
Admission routes1
Has abstractyes

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