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Record W3166952362 · doi:10.1093/protein/gzab014

Recent developments in engineering protein–protein interactions using phage display

2021· review· en· W3166952362 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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueProtein Engineering Design and Selection · 2021
Typereview
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsCanadian Institute for Advanced ResearchUniversity of Guelph
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsPhage displayComputational biologyProtein engineeringProtein designSimilarity (geometry)Drug discoveryProtein–protein interactionComputer scienceStructural similarityBiologyProtein structureBioinformaticsArtificial intelligenceBiochemistry

Abstract

fetched live from OpenAlex

Targeted inhibition of misregulated protein-protein interactions (PPIs) has been a promising area of investigation in drug discovery and development for human diseases. However, many constraints remain, including shallow binding surfaces and dynamic conformation changes upon interaction. A particularly challenging aspect is the undesirable off-target effects caused by inherent structural similarity among the protein families. To tackle this problem, phage display has been used to engineer PPIs for high-specificity binders with improved binding affinity and greatly reduced undesirable interactions with closely related proteins. Although general steps of phage display are standardized, library design is highly variable depending on experimental contexts. Here in this review, we examined recent advances in the structure-based combinatorial library design and the advantages and limitations of different approaches. The strategies described here can be explored for other protein-protein interactions and aid in designing new libraries or improving on previous libraries.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.914
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.077
GPT teacher head0.348
Teacher spread0.270 · 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