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Record W2144417432 · doi:10.1002/prot.22854

Molecular mechanism of β‐sheet self‐organization at water‐hydrophobic interfaces

2010· article· en· W2144417432 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

VenueProteins Structure Function and Bioinformatics · 2010
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersCanadian Institutes of Health Research
KeywordsChemistryMembraneHydrophobic effectBiophysicsLipid bilayerMolecular dynamicsSelf-assemblyPeptideConformational entropyBeta sheetCrystallographyAmphiphileMoleculeOrganic chemistryComputational chemistryBiochemistryCopolymerPolymer

Abstract

fetched live from OpenAlex

The capacity to form β-sheet structure and to self-organize into amyloid aggregates is a property shared by many proteins. Severe neurodegenerative pathologies such as Alzheimer's disease are thought to involve the interaction of amyloidogenic protein oligomers with neuronal membranes. To understand the experimentally observed catalysis of amyloid formation by lipid membranes and other water-hydrophobic interfaces, we examine the physico-chemical basis of peptide adsorption and aggregation in a model membrane using atomistic molecular simulations. Blocked octapeptides with simple, repetitive sequences, (Gly-Ala)₄, and (Gly-Val)₄, are used as models of β-sheet-forming polypeptide chains found in the core of amyloid fibrils. In the presence of an n-octane phase mimicking the core of lipid membranes, the peptides spontaneously partition at the octane-water interface. The adsorption of nonpolar sidechains displaces the peptides' conformational equilibrium from a heterogeneous ensemble characterized by a high degree of structural disorder toward a more ordered ensemble favoring β-hairpins and elongated β-strands. At the interface, peptides spontaneously aggregate and rapidly evolve β-sheet structure on a 10 to 100 ns time scale, while aqueous aggregates remain amorphous. Catalysis of β-sheet formation results from the combination of the hydrophobic effect and of reduced conformational entropy of the polypeptide chain. While the former drives interfacial partition and displaces the conformational equilibrium of monomeric peptides, the planar interface further facilitates β-sheet organization by increasing peptide concentration and reducing the dimensionality of self-assembly from three to two. These findings suggest a general mechanism for the formation of β-sheets on the surface of globular proteins and for amyloid self-organization at hydrophobic interfaces.

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 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 score0.007
Threshold uncertainty score0.573

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)0.0010.000

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 head0.005
GPT teacher head0.219
Teacher spread0.214 · 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