ArticleProtein engineering, design & selection : PEDS2018
Net charge of antibody complementarity-determining regions is a key predictor of specificity.
Article in Protein engineering, design & selection : PEDS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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
48 citing papers in PubMed.
- Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.mAbs · 2026Article
- Senescent-like activated naive B cells contribute to progression to clinical rheumatoid arthritis.Nature aging · 2026Article
- The Evolution of Artificial Intelligence in Antibody Design: From Structure-Based Engineering to Generative Models.Antibodies (Basel, Switzerland) · 2026Review
- Charge-driven antiviral responses enhance autoreactivity in severe COVID-19.Research square · 2026Article
- Impact of heme on the therapeutic efficacy of anti-CD20 antibodies.The Journal of biological chemistry · 2026Article
- Structural insights into antibody responses against influenza A virus in its natural reservoir.bioRxiv : the preprint server for biology · 2026Article
- Engineering Single-Chain Antibody Fragment (scFv) Variants Targeting A Disintegrin and Metalloproteinase-17 (ADAM-17).Biomolecules · 2025Article
- Antibody Polyreactivity: A Challenger of Immune Paradigms.Immunology · 2025Review
- Biophysics of SARS-CoV-2 spike protein's receptor-binding domain interaction with ACE2 and neutralizing antibodies: from computation to functional insights.Biophysical reviews · 2025Review
- Article
- Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies.In silico pharmacology · 2025Article
- AI-enhanced profiling of phage-display-identified anti-TIM3 and anti-TIGIT novel antibodies.Frontiers in immunology · 2025Article
- Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity.Frontiers in immunology · 2025Review
- Directed evolution of drug-like Aβ conformation-specific antibodies.Frontiers in immunology · 2025Article
- Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.Cell reports · 2024Article
- TEMPRO: nanobody melting temperature estimation model using protein embeddings.Scientific reports · 2024Article
- The immunology of B-1 cells: from development to aging.Immunity & ageing : I & A · 2024Review
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
- Single-domain antibodies against SARS-CoV-2 RBD from a two-stage phage screening of universal and focused synthetic libraries.BMC infectious diseases · 2024Article
- Biophysical Analysis of Therapeutic Antibodies in the Early Development Pipeline.Biologics : targets & therapy · 2024Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Specificity is one of the most important and complex properties that is central to both natural antibody function and therapeutic antibody efficacy. However, it has proven extremely challenging to define robust guidelines for predicting antibody specificity. Here we evaluated the physicochemical determinants of antibody specificity for multiple panels of antibodies, including >100 clinical-stage antibodies. Surprisingly, we find that the theoretical net charge of the complementarity-determining regions (CDRs) is a strong predictor of antibody specificity. Antibodies with positively charged CDRs have a much higher risk of low specificity than antibodies with negatively charged CDRs. Moreover, the charge of the entire set of six CDRs is a much better predictor of antibody specificity than the charge of individual CDRs, variable domains (VH or VL) or the entire variable fragment (Fv). The best indicators of antibody specificity in terms of CDR amino acid composition are reduced levels of arginine and lysine and increased levels of aspartic and glutamic acid. Interestingly, clinical-stage antibodies with negatively charged CDRs also have a lower risk for poor biophysical properties in general, including a reduced risk for high levels of self-association. These findings provide powerful guidelines for predicting antibody specificity and for identifying safe and potent antibody therapeutics.
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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.