ArticleJournal of structural biology2014
Structure-based non-canonical amino acid design to covalently crosslink an antibody-antigen complex.
Article in Journal of structural biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Design, Construction, and Validation of a Yeast-Displayed Chemically Expanded Antibody Library.ACS synthetic biology · 2025Article
- Design, Construction, and Validation of a Yeast-Displayed Chemically Expanded Antibody Library.bioRxiv : the preprint server for biology · 2024Article
- Single-Cell B-Cell Sequencing to Generate Natively Paired scFab Yeast Surface Display Libraries.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Yeast Display Enables Identification of Covalent Single-Domain Antibodies against Botulinum Neurotoxin Light Chain A.ACS chemical biology · 2022Article
- Biosynthesis and Genetic Incorporation of 3,4-Dihydroxy-L-Phenylalanine into Proteins in Escherichia coli.Journal of molecular biology · 2022Article
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation.Journal of visualized experiments : JoVE · 2018Article
- A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design.PLoS computational biology · 2017Article
- Accurate Structure Prediction of CDR H3 Loops Enabled by a Novel Structure-Based C-Terminal Constraint.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Protocols for Molecular Modeling with Rosetta3 and RosettaScripts.Biochemistry · 2016Review
- The origin of CDR H3 structural diversity.Structure (London, England : 1993) · 2015Article
- Blind prediction performance of RosettaAntibody 3.0: grafting, relaxation, kinematic loop modeling, and full CDR optimization.Proteins · 2014Article
- Protein folding and de novo protein design for biotechnological applications.Trends in biotechnology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Engineering antibodies to utilize non-canonical amino acids (NCAA) should greatly expand the utility of an already important biological reagent. In particular, introducing crosslinking reagents into antibody complementarity determining regions (CDRs) should provide a means to covalently crosslink residues at the antibody-antigen interface. Unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic detail. Computer-aided antibody design can potentially greatly restrict the number of variants that must be explored in order to identify successful crosslinking sites. We have therefore used Rosetta to guide the introduction of an oxidizable crosslinking NCAA, l-3,4-dihydroxyphenylalanine (l-DOPA), into the CDRs of the anti-protective antigen scFv antibody M18, and have measured crosslinking to its cognate antigen, domain 4 of the anthrax protective antigen. Computed crosslinking distance, solvent accessibility, and interface energetics were three factors considered that could impact the efficiency of l-DOPA-mediated crosslinking. In the end, 10 variants were synthesized, and crosslinking efficiencies were generally 10% or higher, with the best variant crosslinking to 52% of the available antigen. The results suggest that computational analysis can be used in a pipeline for engineering crosslinking antibodies. The rules learned from l-DOPA crosslinking of antibodies may also be generalizable to the formation of other crosslinked interfaces and complexes.
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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.