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Record W4399506620 · doi:10.1039/d4sc01785d

Non-Aufbau electronic structure in radical enzymes and control of the highly reactive intermediates

2024· article· en· W4399506620 on OpenAlexafffund
M. Hossein Khalilian, Gino A. DiLabio

Bibliographic record

VenueChemical Science · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPorphyrin Metabolism and Disorders
Canadian institutionsUniversity of British Columbia, Okanagan CampusUniversity of British Columbia
FundersAlliance de recherche numérique du CanadaNatural Sciences and Engineering Research Council of CanadaUniversity of British ColumbiaCanada Foundation for Innovation
KeywordsReactive intermediateChemistryRadicalEnzymeCombinatorial chemistryStereochemistryBiochemistryCatalysis

Abstract

fetched live from OpenAlex

-enzymes is initiated through the formation of the 5'-deoxyadenosyl (Ado˙) moiety, a primary carbon-centred radical, which must migrate up to 8 Å to reach the target substrate to engage in the next step of the catalytic process, a hydrogen atom abstraction. Our calculations reveal that Ado˙ within the protein environment exhibits an unusual non-Aufbau electronic structure in which the singly occupied molecular orbital is lower in energy than the doubly occupied orbitals, an uncommon phenomenon known as SOMO-HOMO inversion (SHI). We find that the magnitude of SHI in the initially formed Ado˙ is larger compared to when the Ado˙ is near the intended substrate, leading to the former being relatively less reactive. The modulation of the SHI originates from Coulombic interactions of a quantum nature between a negative charge on a conserved glutamate residue and the spin on the Ado˙. Our findings support a novel hypothesis that these enzymes utilize this quantum Coulombic effect as a means of maintaining exquisite control over the chemistry of highly reactive radical intermediates in enzyme active sites.

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 score0.007
Threshold uncertainty score0.299

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 studies0.0000.001
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 head0.001
GPT teacher head0.208
Teacher spread0.207 · 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
Published2024
Admission routes2
Has abstractyes

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