ArticleFrontiers in immunology2018
Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- H3BERTa: A CDR-H3-specific language model for antibody repertoire analysis.Patterns (New York, N.Y.) · 2026Article
- Observation of redistribution for local conformational dynamics in cross-reactive antibody design.Journal of biochemistry · 2026Article
- AFM-Based Single-Molecule Force Spectroscopy of PEG-Anti-PEG Antibody Interactions.ACS applied bio materials · 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
- Enhancing antibody-antigen interaction prediction with atomic flexibility.PLoS computational biology · 2025Article
- Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.Protein science : a publication of the Protein Society · 2025Article
- Applying computational protein design to therapeutic antibody discovery - current state and perspectives.Frontiers in immunology · 2025Review
- Antibodies and cryptographic hash functions: quantifying the specificity paradox.Frontiers in immunology · 2025Article
- Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining.Nature communications · 2024Article
- Extended Conformational Selection in the Antigen-Antibody Interaction of the PfAMA1 Protein.The journal of physical chemistry. B · 2024Article
- AbMelt: Learning antibody thermostability from molecular dynamics.Biophysical journal · 2024Article
- The immunology of B-1 cells: from development to aging.Immunity & ageing : I & A · 2024Review
- De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics.ACS chemical biology · 2024Article
- Biochemical and biophysical characterization of natural polyreactivity in antibodies.Cell reports · 2023Article
- Arginine cluster introduction on framework region in anti-lysozyme antibody improved association rate constant by changing conformational diversity of CDR loops.Protein science : a publication of the Protein Society · 2023Article
- Structural Characterization of Nanobodies during Germline Maturation.Biomolecules · 2023Article
- Structural modeling of antibody variable regions using deep learning-progress and perspectives on drug discovery.Frontiers in molecular biosciences · 2023Review
- Design of nanobody-based bispecific constructs byComputational and structural biotechnology journal · 2023Article
- Probing Conformational Dynamics of Antibodies with Geometric Simulations.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody's antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.
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