ArticleProtein engineering, design & selection : PEDS2011
Probing the stability-limiting regions of an antibody single-chain variable fragment: a molecular dynamics simulation study.
Article in Protein engineering, design & selection : PEDS, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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, 27 citations in OpenAlex.
- A single-domain antibody library based on a stability-engineered human VH3 scaffold.Scientific reports · 2024Article
- Controlling CAR-T cell activity and specificity with synthetic SparX adapters.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Comparison of the pH- and thermally-induced fluctuations of a therapeutic antibody Fab fragment by molecular dynamics simulation.Computational and structural biotechnology journal · 2021Article
- Strategies to Address Chimeric Antigen Receptor Tonic Signaling.Molecular cancer therapeutics · 2018Review
- Determinants of the assembly and function of antibody variable domains.Scientific reports · 2017Article
- Nanoyeast and Other Cell Envelope Compositions for Protein Studies and Biosensor Applications.ACS applied materials & interfaces · 2016Review
- Enhancing Protein Capture Using a Combination of Nanoyeast Single-Chain Fragment Affinity Reagents and Alternating Current Electrohydrodynamic Forces.Analytical chemistry · 2015Article
- Advances in Antibody Design.Annual review of biomedical engineering · 2015Review
- Article
- Effective therapeutic approach for head and neck cancer by an engineered minibody targeting the EGFR receptor.PloS one · 2014Article
- Structure Based Refinement of a Humanized Monoclonal Antibody That Targets Tumor Antigen Disialoganglioside GD2.Frontiers in immunology · 2014Article
- Directed evolution of a fluorogen-activating single chain antibody for function and enhanced brightness in the cytoplasm.Molecular biotechnology · 2013Article
- Computer-aided antibody design.Protein engineering, design & selection : PEDS · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Antibody single-chain variable fragments (scFvs) offer particular advantages over the full-size antibodies, including easy expression, efficient local concentration and fast body clearance. However, scFvs typically show low thermal stability that limits their biomedical and biotechnological applications. In this study, we examined the thermal stability of the human and murine vascular endothelial growth factor antibody scFv fragment by molecular dynamics simulations. A consistent observation was the dissociation of the light-chain (VL) and heavy-chain (VH) domains and loss of the native structures of both domains in the simulations at the elevated temperatures. The stability-limiting structural elements in the protein were revealed from the detailed analyses on the native contacts. We found that dissociation of the VL-VH domains was the first event leading to the unfolding of the native structure of the protein and the disruption of the VL-VH interface was largely due to the break of the interfacial hydrophobic and aromatic interactions while the hydrogen-bonding interaction between Gln38 in VL and Gln39 in VH remained. Within the β-barrel structure of the VL and VH domains, β-strands β6, β2 and β11 appeared to be the least stable. In addition, we found that the VH domain was more thermally resistant than the VL domain. Based on these findings, we discussed potential strategies to improve the stability of this therapeutically important scFv fragment.
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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.