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Record W4410218279 · doi:10.1021/acs.biomac.5c00097

Applying Computational Protein Design to Engineer Affibodies for Affinity-controlled Delivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor

2025· article· en· W4410218279 on OpenAlexafffund
Justin E. Svendsen, Madeleine R. Ford, Chandler L. Asnes, Sang Cheul Oh, Jonathan Dorogin, Karly M. Fear, Johnathan R. O’Hara-Smith, Lauren O. Chisholm, Sophia R. Phillips, Michael J. Harms, Parisa Hosseinzadeh, Marian H. Hettiaratchi

Bibliographic record

VenueBiomacromolecules · 2025
Typearticle
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsImpact
FundersDivision of Graduate EducationNational Institute of Biomedical Imaging and BioengineeringNational Institute of General Medical SciencesNational Heart, Lung, and Blood InstituteNatural Sciences and Engineering Research Council of CanadaUniversity of OregonOregon Health and Science UniversityNational Institutes of HealthNational Science Foundation
KeywordsGrowth factorChemistryVascular endothelial growth factorCell biologyBiochemistryPlatelet-derived growth factorPlateletVascular endothelial growth factor ABiophysicsBiologyImmunologyVEGF receptorsCancer researchPlatelet-derived growth factor receptorReceptor

Abstract

fetched live from OpenAlex

Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) play coordinated roles in angiogenesis. However, current biomaterial delivery vehicles for these proteins have a limited ability to precisely control the kinetics of protein release, preventing systematic exploration of their temporal effects. Here, we combined yeast surface display and computational protein design to engineer eight VEGF-specific and PDGF-specific protein binders called affibodies with a broad range of affinities for controlled protein release. Soluble affibodies modulated protein bioactivity as evidenced by changes in VEGF-induced endothelial cell proliferation and luminescent output of a PDGF-responsive cell line. Affibody-conjugated hydrogels enabled tunable protein release over 7 days. VEGF and PDGF released from affibody-conjugated hydrogels exhibited higher bioactivity than proteins released from hydrogels without affibodies, suggesting that these engineered affinity interactions could prolong protein bioactivity. This work underscores the power of computational protein design to enhance biomaterial functionality, creating a platform for tunable protein delivery.

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 score0.030
Threshold uncertainty score0.952

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.025
GPT teacher head0.283
Teacher spread0.258 · 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

Citations4
Published2025
Admission routes2
Has abstractyes

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