Data di Pubblicazione:
2022
Citazione:
Fragment-based computational design of antibodies targeting structured epitopes / M. Aguilar Rangel, A. Bedwell, E. Costanzi, R.J. Taylor, R. Russo, G.J.L. Bernardes, S. Ricagno, J. Frydman, M. Vendruscolo, P. Sormanni. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 8:45(2022 Nov 11), pp. eabp9540.1-eabp9540.14. [10.1126/sciadv.abp9540]
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 com-binatorial 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 do-main 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 dis-cuss 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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Aguilar Rangel, A. Bedwell, E. Costanzi, R.J. Taylor, R. Russo, G.J.L. Bernardes, S. Ricagno, J. Frydman, M. Vendruscolo, P. Sormanni
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