ArticleJournal of molecular biology2012
Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- Deep learning-enabled scaffolding of spatial arrays of PfCSP epitopes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- HIV Membrane-Proximal External Region Scaffolded Immunogen as Killed Whole-Cell Genome-Reduced Vaccines.Viruses · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- AntiBMPNN: Structure-Guided Graph Neural Networks for Precision Antibody Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structure-guided design and evaluation of CRM197-scaffolded vaccine targeting GnRH for animal immunocastration.Applied microbiology and biotechnology · 2024Article
- Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation.ACS infectious diseases · 2024Article
- Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.Nature communications · 2023Article
- Heterologous sarbecovirus receptor binding domains as scaffolds for SARS-CoV-2 receptor binding motif presentation.bioRxiv : the preprint server for biology · 2023Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Adaptation-proof SARS-CoV-2 vaccine design.Advanced functional materials · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
- Toward rational vaccine engineering.Advanced drug delivery reviews · 2022Review
- Protein Assembly by Design.Chemical reviews · 2021Review
- Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate.Vaccines · 2021Article
- Review
- On the irrationality of rational design of an HIV vaccine in light of protein intrinsic disorder.Archives of virology · 2021Review
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- Exploring the binding of rationally engineered tandem-repeat proteins to E3 ubiquitin ligase Keap1.Protein engineering, design & selection : PEDS · 2021Article
- Computational design and experimental optimization of protein binders with prospects for biomedical applications.Protein engineering, design & selection : PEDS · 2021Review
- Structure-Guided Design of a Synthetic Mimic of an Endothelial Protein C Receptor-Binding PfEMP1 Protein.mSphere · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
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Abstract
Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel "epitope-scaffold" antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method-backbone grafting of linear motifs-that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.