Data di Pubblicazione:
2021
Citazione:
Fragment-based computational design of antibodies targeting structured epitopes / M. Aguilar Rangel, A. Bedwell, E. Costanzi, R. Taylor, R. Russo, G.J.L. Bernardes, S. Ricagno, J. Frydman, M. Vendruscolo, P. Sormanni. - (2021). [10.1101/2021.03.02.433360]
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 specific 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 characterisation showed that all
designs are highly stable, and bind their intended targets with affinities in the nanomolar
range without any in vitro affinity maturation. We further show that a high-resolution
input antigen structure is not required, as our method yields similar predictions when the
input is a crystal structure or a computer-generated model. This computational
procedure, which readily runs on a laptop, provides the starting point for the rapid
generation of lead antibodies binding to pre-selected epitopes.
Tipologia IRIS:
24 - Pre-print
Elenco autori:
M. Aguilar Rangel, A. Bedwell, E. Costanzi, R. Taylor, R. Russo, G.J.L. Bernardes, S. Ricagno, J. Frydman, M. Vendruscolo, P. Sormanni
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