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Record W3015117291 · doi:10.1101/2020.04.01.020420

Mapping shifts in nanopore signal to changes in protein and protein-DNA conformation

2020· preprint· en· W3015117291 on OpenAlexafffund
Autumn Carlsen, Vincent Tabard‐Cossa

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldEngineering
TopicNanopore and Nanochannel Transport Studies
Canadian institutionsUniversity of Ottawa
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsNanoporeStreptavidinBiophysicsSIGNAL (programming language)DNABiotinylationNanopore sequencingNanotechnologyChemistryChemical physicsCrystallographyMaterials scienceBiotinBiologyBiochemistryComputer science

Abstract

fetched live from OpenAlex

ABSTRACT Solid-state nanopores have been used extensively in biomolecular studies involving DNA and proteins. However, the interpretation of signals generated by the translocation of proteins or protein-DNA complexes remains challenging. Here, we investigate the behavior of monovalent streptavidin and the complex it forms with short biotinylated DNA over a range of nanopore sizes, salts and voltages. We describe a simple geometric model that is broadly applicable and employ it to explain observed variations in conductance blockage and dwell time with experimental conditions. The general approach developed here underscores the value of nanopore-based protein analysis and represents progress toward the interpretation of complex translocation signals. STATEMENT OF SIGNIFICANCE Nanopore sensing allows investigation of biomolecular structure in aqueous solution, including electricfield-induced changes in protein conformation. This nanopore-based study probes: (1) the tetramerdimer transition of streptavidin, observing the effects of increasing voltage with varying salt type and concentration; (2) the possible conformational states of DNA-streptavidin complexes when confined inside a pore. We describe a broadly applicable geometric approach that maps stepwise changes in the nanopore signal to real-time conformational transitions. These results represent progress toward accurate interpretation of nanopore signals generated by molecular complexes.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

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)0.0010.000

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 head0.014
GPT teacher head0.191
Teacher spread0.177 · 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 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

Citations7
Published2020
Admission routes2
Has abstractyes

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