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Record W4405208134 · doi:10.1177/00368504241266357

The multifaceted helical net of amphipathic alpha-helices; the next dimension of the helical peptide wheel

2024· article· en· W4405208134 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

VenueScience Progress · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChemical Synthesis and Analysis
Canadian institutionsUniversity of Alberta
FundersCanadian Institutes of Health ResearchAmerican Heart Association
KeywordsAmphiphilePeptideChemistryHelix (gastropod)Peptide sequenceAmino acidAlpha helixBiophysicsProtein structureCrystallographyStereochemistryBiochemistryCopolymerBiologyOrganic chemistryPolymer

Abstract

fetched live from OpenAlex

The amphipathic nature of helical proteins is crucial to their binding features across a broad spectrum of physiological examples, including heat-shock proteins and hyaluronic acid (HA) receptor binding. By taking advantage of the amphipathic balance of amino acids and their presentation in helical faces, novel synthetic peptides can be designed to improve biofunctionality. We present a new approach for designing synthetic alpha helical peptides using a multifaceted analysis, which allows for new bioengineering designs of amphipathic alpha helices. Amphipathic helical peptides were presented with distinct hydrophobic and hydrophilic faces; two series of analogs, namely, peptides AX9 and AX7, were designed to contain a hydrophobic and hydrophilic face, respectively. The presence of one series of peptides exhibited a distinct hydrophobic face and the second series exhibited a distinct hydrophilic face, which was corroborated with reversed-phase chromatography (C8). Using a multifaceted approach to analyze the potential faces of an amphipathic helix, we demonstrated that these helices contain seven distinct “side-viewed” helical faces (based on the hydrophobic face of the AXP series of analogs), which provides additional spatial dimensional information beyond the averaging effect of the hydrophobic moment generated from the “top-down” view of a helical wheel. Furthermore, we cross-compared our recently published HA-binding peptide in this manner to demonstrate that the most significant binding was related to (1) balanced amphipathicity and (2) a distribution of the key HA-binding domain B1(X 7 )B2 presented spatially. For example, our most effective peptide binder 17x-3 has five of seven faces with B1(X 7 )B2 domains, while the positive control mPEP35 has three, which reflects a lower affinity. With such a tool, one is able to map helical peptides on an additional dimension to characterize and redesign fundamental amphipathic properties among other critical characteristics, such as sugar and glycan binding, which is a fundamental characteristic feature of cellular interactions in almost every biological system.

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)0.001
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 score0.025
Threshold uncertainty score0.860

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.014
GPT teacher head0.281
Teacher spread0.268 · 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