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Record W4385239172 · doi:10.1002/hlca.202300097

Structural Determinants of the Binding and Activation of Estrogen Receptor α by Phenolic Thieno[2,3‐ <i>d</i> ]pyrimidines

2023· article· en· W4385239172 on OpenAlexfundno aff
Vamshikrishna Reddy Sammeta, Brian Anderson, John D. Norris, Chad Torrice, Carstyn Joiner, Shubin Liu, Haoxi Li, Konstantin I. Popov, Sean W. Fanning, Donald P. McDonnell, Timothy M. Willson

Bibliographic record

VenueHelvetica Chimica Acta · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEstrogen and related hormone effects
Canadian institutionsnot available
FundersJanssen BiotechBiological and Environmental ResearchGenentechOntario Genomics InstituteEuropean Federation of Pharmaceutical Industries and AssociationsNational Institutes of HealthOntario GenomicsMerck KGaAGenome CanadaLoyola University ChicagoBayerMcGill UniversityTakeda Pharmaceuticals U.S.A.PfizerBristol-Myers SquibbNorth Carolina Biotechnology CenterGenentech FoundationBoehringer IngelheimArgonne National LaboratoryU.S. Department of EnergyU.S. Department of Defense
KeywordsChemistryEstrogen receptorPhenolsStereochemistryReceptorEstrogenNonsteroidalMolecular dynamicsBiochemistryComputational chemistryInternal medicine

Abstract

fetched live from OpenAlex

Abstract Synthetic, structural, and computational approaches were used to solve the puzzle as to how a phenolic nonsteroidal estrogen 1 with only a single H‐bond to its receptor was more potent than an isomer 2 which formed an intricate network of H‐bonds. Synthesis of a series of substituted phenols revealed that p K a was not a determinant of estrogenic activity. First‐principles calculation also failed to explain the difference in activity of 1 and 2 . Molecular dynamics revealed that 1 formed a more stable receptor complex compared to 2 , which may explain its increased activity despite forming fewer apparent H‐bonds with the protein.

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 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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.364

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 head0.008
GPT teacher head0.237
Teacher spread0.229 · 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 teacher head, 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
Published2023
Admission routes1
Has abstractyes

Explore more

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