ArticleProtein engineering, design & selection : PEDS2015
Co-evolution of affinity and stability of grafted amyloid-motif domain antibodies.
Article in Protein engineering, design & selection : PEDS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- Multidimensional maturation of antibody variable domains with machine-learning assistance.mAbs · 2026Article
- Structure-Guided Affinity Maturation of an Antibody Fragment for Gold-Surface Biosensing of N‑Terminal Pro-B-Type Natriuretic Peptide.ACS omega · 2026Article
- Optimization of synthetic human VProtein science : a publication of the Protein Society · 2025Article
- Fragment-based computational design of antibodies targeting structured epitopes.Science advances · 2022Article
- Co-optimization of therapeutic antibody affinity and specificity using machine learning models that generalize to novel mutational space.Nature communications · 2022Article
- GroEL-A Versatile Chaperone for Engineering and a Plethora of Applications.Biomolecules · 2022Review
- Engineering Strategies to Overcome the Stability-Function Trade-Off in Proteins.ACS synthetic biology · 2022Review
- Affinity and Stability Analysis of Yeast Displayed Proteins.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Assessment of Therapeutic Antibody Developability by Combinations of In Vitro and In Silico Methods.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Delicate balance among thermal stability, binding affinity, and conformational space explored by single-domain VScientific reports · 2021Article
- Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.bioRxiv : the preprint server for biology · 2020Article
- Directed evolution methods for overcoming trade-offs between protein activity and stability.AIChE journal. American Institute of Chemical Engineers · 2020Article
- Nature-inspired design and evolution of anti-amyloid antibodies.The Journal of biological chemistry · 2019Article
- Single-Domain Antibodies as Therapeutic and Imaging Agents for the Treatment of CNS Diseases.Antibodies (Basel, Switzerland) · 2019Review
- Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility.Biochemical engineering journal · 2018Article
- Improvement of antibody affinity by introduction of basic amino acid residues into the framework region.Biochemistry and biophysics reports · 2018Article
- Designing macrocyclic disulfide-rich peptides for biotechnological applications.Nature chemical biology · 2018Article
- Arginine mutations in antibody complementarity-determining regions display context-dependent affinity/specificity trade-offs.The Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
An attractive approach for designing lead antibody candidates is to mimic natural protein interactions by grafting peptide recognition motifs into the complementarity-determining regions (CDRs). We are using this approach to generate single-domain (VH) antibodies specific for amyloid-forming proteins such as the Alzheimer's Aβ peptide. Here, we use random mutagenesis and yeast surface display to improve the binding affinity of a lead VH domain grafted with Aβ residues 33-42 in CDR3. Interestingly, co-selection for improved Aβ binding and VH display on the surface of yeast yields antibody domains with improved affinity and reduced stability. The highest affinity VH domains were strongly destabilized on the surface of yeast as well as unfolded when isolated as autonomous domains. In contrast, stable VH domains with improved affinity were reliably identified using yeast surface display by replacing the display antibody that recognizes a linear epitope tag at the terminus of both folded and unfolded VH domains with a conformational ligand (Protein A) that recognizes a discontinuous epitope on the framework of folded VH domains. Importantly, we find that selection for improved stability using Protein A without simultaneous co-selection for improved Aβ binding leads to strong enrichment for stabilizing mutations that reduce antigen binding. Our findings highlight the importance of simultaneously optimizing affinity and stability to improve the rapid isolation of well-folded and specific antibody fragments.
Indexed as
Identifiers
What OpenQuestion holds
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.