Fragment-based computational design of antibodies targeting structured epitopes.
Sci Adv
; 8(45): eabp9540, 2022 11 11.
Article
in English
| MEDLINE | ID: covidwho-2119147
ABSTRACT
De novo design methods hold the promise of reducing the time and cost of antibody discovery while enabling the facile and precise targeting of predetermined epitopes. Here, we describe a fragment-based method for the combinatorial design of antibody binding loops and their grafting onto antibody scaffolds. We designed and tested six single-domain antibodies targeting different epitopes on three antigens, including the receptor-binding domain of the SARS-CoV-2 spike protein. Biophysical characterization showed that all designs are stable and bind their intended targets with affinities in the nanomolar range without in vitro affinity maturation. We further discuss how a high-resolution input antigen structure is not required, as similar predictions are obtained when the input is a crystal structure or a computer-generated model. This computational procedure, which readily runs on a laptop, provides a starting point for the rapid generation of lead antibodies binding to preselected epitopes.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
/
Antibodies, Monoclonal
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Sci Adv
Year:
2022
Document Type:
Article
Affiliation country:
Sciadv.abp9540
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