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Record W4392052723 · doi:10.54254/2977-3903/6/2024056

Protein structure prediction based on deep learning: HER2 in complex with a covalent inhibitor

2024· article· en· W4392052723 on OpenAlexaff
Wenyi Yao

Bibliographic record

VenueAdvances in Engineering Innovation · 2024
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsWestern University
Fundersnot available
KeywordsChemistryCovalent bondDocking (animal)MonomerProtein structureBiochemistryBiophysicsCancer researchBiologyMedicine

Abstract

fetched live from OpenAlex

HER2 protein overexpression is associated with the malignant degree and poor prognosis of breast cancer. HER2 levels are elevated in 20% of breast tumors. Several covalent tyrosine kinase inhibitors have been found to reduce tumor cell survival and proliferation in vitro and inhibit downstream HER2 signaling. In the field of protein structure prediction, AlphaFold2, which achieved excellent results in CASP14, can periodically predict protein structures with atomic precision in the absence of similar protein structures. In this study, AlphaFold2 was used to predict the monomeric structure of the HER2 protein. This predicted structure was compared to the conformation of HER2 in complex with a covalent inhibitor, allowing for an examination of the conformational changes induced by the inhibitor. By combining the conformational changes of HER2 protein with the docking results of Protein-Ligand Interaction Profiler, other potential binding sites were identified, which could further reveal the mechanism of drug discovery.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.009
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
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 head0.009
GPT teacher head0.261
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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
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

Citations0
Published2024
Admission routes1
Has abstractyes

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