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Assessing and Engineering Antibody Stability Using Experimental and Computational Methods

Zhang, Cheng; Dalby, Paul Anthony; (2023) Assessing and Engineering Antibody Stability Using Experimental and Computational Methods. Methods in Molecular Biology , 2552 pp. 165-197. 10.1007/978-1-0716-2609-2_9. Green open access

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Abstract

Engineering increased stability into antibodies can improve their developability. While a range of properties need to be optimized, thermal stability and aggregation are two key factors that affect the antibody yield, purity, and specificity throughout the development and manufacturing pipeline. Therefore, an ideal goal would be to apply protein engineering methods early-on, such as in parallel to affinity maturation, to screen out potential drug molecules with the desired conformational and colloidal stability. This chapter introduces our methods to computationally characterize an antibody Fab fragment, propose stabilizing variants, and then experimentally verify these predictions.

Type: Article
Title: Assessing and Engineering Antibody Stability Using Experimental and Computational Methods
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-1-0716-2609-2_9
Publisher version: https://doi.org/10.1007/978-1-0716-2609-2_9
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Antibodies, Antibody Affinity, Immunoglobulin Fab Fragments, Molecular Conformation, Protein Engineering, Protein Stability, Aggregation, Antibody, B-factor, Entropy, Fab, Molecular dynamics (Gromacs), Rosetta, Tm
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10159884
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