6Z3X

Crystal structure of the designed antibody DesAb-anti-HSA-P1

Summary for 6Z3X

• Entry DOI: 10.2210/pdb6z3x/pdb
• Descriptor: DesAb-anti-HSA-P1, CACODYLATE ION, IMIDAZOLE, ... (5 entities in total)
• Functional Keywords: protein design, artificial antibody, specific interaction, immune system
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 30981.03

Authors

Costanzi, E.,Sormanni, P.,Ricagno, S. (deposition date: 2020-05-22, release date: 2021-03-31, Last modification date: 2024-11-13)

Primary citation

Aguilar Rangel, M.,Bedwell, A.,Costanzi, E.,Taylor, R.J.,Russo, R.,Bernardes, G.J.L.,Ricagno, S.,Frydman, J.,Vendruscolo, M.,Sormanni, P.
Fragment-based computational design of antibodies targeting structured epitopes.
Sci Adv, 8:eabp9540-eabp9540, 2022

PubMed 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.

PubMed: 36367941
DOI: 10.1126/sciadv.abp9540

Experimental method

X-RAY DIFFRACTION (1.74 Å)