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Record W3190330215 · doi:10.1016/j.omtn.2021.07.015

The role of SAXS and molecular simulations in 3D structure elucidation of a DNA aptamer against lung cancer

2021· article· en· W3190330215 on OpenAlexaff
Dmitry Morozov, Vladimir Mironov, Roman V. Moryachkov, Irina A. Shchugoreva, Polina V. Artyushenko, Galina S. Zamay, Olga S. Kolovskaya, Tatiana N. Zamay, Alexey V. Krat, Dmitry Molodenskiy, V. N. Zabluda, Dmitry V. Veprintsev, Alexey E. Sokolov, Р. А. Зуков, Maxim V. Berezovski, Felix N. Tomilin, Dmitri G. Fedorov, Yuri Alexeev, Anna S. Kichkailo

Bibliographic record

VenueMolecular Therapy — Nucleic Acids · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced biosensing and bioanalysis techniques
Canadian institutionsUniversity of Ottawa
FundersRussian Foundation for Basic ResearchJapan Society for the Promotion of ScienceHorizon 2020 Framework ProgrammeTomsk State UniversityRussian Science FoundationBundesministerium für Bildung und ForschungOffice of ScienceDeutsches Elektronen-SynchrotronArgonne National LaboratoryU.S. Department of EnergyEuropean CommissionChina Scholarship Council
KeywordsAptamerSmall-angle X-ray scatteringOligonucleotideDNAChemistryMoleculeRNAMolecular dynamicsFragment molecular orbitalBiophysicsScatteringBiologyMolecular orbitalBiochemistryGeneComputational chemistryMolecular biologyPhysics

Abstract

fetched live from OpenAlex

Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here, we present a general optimization procedure for finding the most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated LC-18 (LC-18t) aptamer LC-18t was developed. A three-dimensional (3D) shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes.

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 score0.030
Threshold uncertainty score0.547

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 head0.004
GPT teacher head0.255
Teacher spread0.252 · 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

Citations28
Published2021
Admission routes1
Has abstractyes

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