ArticleProtein engineering, design & selection : PEDS2022
Bispecific antibodies-effects of point mutations on CH3-CH3 interface stability.
Article in Protein engineering, design & selection : PEDS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 4 citations in OpenAlex.
- Review
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Engineering Fc heterodimerization via asymmetric β-strand reconfiguration for bispecific antibody assembly.Journal of biological engineering · 2026Article
- Hybrid Mass Spectrometry Applied across the Production of Antibody Biotherapeutics.Journal of the American Society for Mass Spectrometry · 2025Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines.Antibodies (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
A new format of therapeutic proteins is bispecific antibodies, in which two different heavy chains heterodimerize to obtain two different binding sites. Therefore, it is crucial to understand and optimize the third constant domain (CH3-CH3) interface to favor heterodimerization over homodimerization, and to preserve the physicochemical properties, as thermal stability. Here, we use molecular dynamics simulations to investigate the dissociation process of 19 CH3-CH3 crystal structures that differ from each other in few point mutations. We describe the dissociation of the dimeric interface as a two-steps mechanism. As confirmed by a Markov state model, apart from the bound and the dissociated state, we observe an additional intermediate state, which corresponds to an encounter complex. The analysis of the interdomain contacts reveals key residues that stabilize the interface. We expect that our results will improve the understanding of the CH3-CH3 interface interactions and thus advance the developability and design of new antibodies formats.
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Registered trials
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