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Record W3057625252 · doi:10.1016/j.celrep.2020.108037

Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments

2020· article· en· W3057625252 on OpenAlexafffund
Edurne Rujas, Sara Insausti, Daniel P. Leaman, Pablo Carravilla, Saul González-Resines, Valérie Monceaux, Rubén Sánchez‐Eugenia, Miguel García‐Porras, Ibón Iloro, Lei Zhang, Félix Elortza, Jean‐Philippe Julien, Asier Sáez‐Cirión, Michael B. Zwick, Christian Eggeling, Akio Ojida, Cármen Domene, José M. M. Caaveiro, José L. Nieva

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersBiotechnology and Biological Sciences Research CouncilNational Institute of Allergy and Infectious DiseasesMedical Research CouncilEuropean CommissionEuskal Herriko UnibertsitateaCanada Research ChairsEusko JaurlaritzaDeutsche ForschungsgemeinschaftWolfson FoundationJapan Agency for Medical Research and DevelopmentJapan Society for the Promotion of ScienceJames B. Pendleton Charitable TrustMinisterio de Ciencia e InnovaciónWellcome Trust
KeywordsEpitopeMembraneAntibodyChemistryGlycoproteinMolecular recognitionBiophysicsAntigenMembrane proteinHuman immunodeficiency virus (HIV)Cell membraneLipid bilayerCell biologyVirologyBiochemistryBiologyMoleculeImmunology

Abstract

fetched live from OpenAlex

The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.

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 score0.011
Threshold uncertainty score0.204

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 head0.027
GPT teacher head0.280
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

Citations15
Published2020
Admission routes2
Has abstractyes

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