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Record W4281671605 · doi:10.1080/08927022.2022.2080822

Deciphering the structural and functional impact of Q657L mutation in <i>NLRC4</i> using computational methods

2022· article· en· W4281671605 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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueMolecular Simulation · 2022
Typearticle
Languageen
FieldMedicine
TopicInfluenza Virus Research Studies
Canadian institutionsnot available
FundersMinistry of Health, British Columbia
KeywordsNLRC4In silicoMutantMolecular dynamicsInflammasomeHomology modelingMutationChemistryBiologyBiophysicsGeneticsBiochemistryCaspase 1Computational chemistryReceptorEnzymeGene

Abstract

fetched live from OpenAlex

The NLR family caspase recruitment domain-containing protein 4 (NLRC4) inflammasome regulates the inflammatory response. Upregulation of NLRC4 inflammasome has been associated with bacterial infections, cancers, and autoinflammatory disorders (AIDs). The Q657L mutation in the NLRC4 causes AID. However, the structural change upon Q657L mutation at the atomic level has not been clearly understood. In this study, we employed in silico predictions along with molecular dynamics (MD) simulations of the homology modelled human wild-type and mutant NLRC4 structures in the resting and activated state to investigate the impact of Q657L mutation on the structural and dynamic changes of NLRC4 protein. The Q657L mutation was predicted to be deleterious by various in silico prediction tools. The MD simulation results demonstrated that the mutation increased the stability of the compactly folded structure and decreased flexibility in the resting state. In the activated state, the stably folded mutant structure had increased solvent accessible surface area, intermolecular hydrogen bonds and binding pocket volume. In addition, the principal component analysis showed that the mutant structures had reduced dynamics in both states. These findings provide insights into structural and dynamic changes of NLRC4 protein due to Q657L mutation at the atomic level.

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: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.264
Threshold uncertainty score0.237

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 head0.102
GPT teacher head0.479
Teacher spread0.377 · 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