5VLI

Computationally designed inhibitor peptide HB1.6928.2.3 in complex with influenza hemagglutinin (A/PuertoRico/8/1934)

Summary for 5VLI

• Entry DOI: 10.2210/pdb5vli/pdb
• Descriptor: Hemagglutinin, Computationally designed peptide HB1.6928.2.3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: inhibitor, protein design, influenza, hemagglutinin, viral protein-de novo protein complex, viral protein/de novo protein
• Biological source: Influenza A virus (strain A/Puerto Rico/8/1934 H1N1); More
• Total number of polymer chains: 3
• Total formula weight: 63147.79

Authors

Bernard, S.M.,Wilson, I.A. (deposition date: 2017-04-25, release date: 2017-09-27, Last modification date: 2024-10-23)

Primary citation

Chevalier, A.,Silva, D.A.,Rocklin, G.J.,Hicks, D.R.,Vergara, R.,Murapa, P.,Bernard, S.M.,Zhang, L.,Lam, K.H.,Yao, G.,Bahl, C.D.,Miyashita, S.I.,Goreshnik, I.,Fuller, J.T.,Koday, M.T.,Jenkins, C.M.,Colvin, T.,Carter, L.,Bohn, A.,Bryan, C.M.,Fernandez-Velasco, D.A.,Stewart, L.,Dong, M.,Huang, X.,Jin, R.,Wilson, I.A.,Fuller, D.H.,Baker, D.
Massively parallel de novo protein design for targeted therapeutics.
Nature, 550:74-79, 2017

PubMed Abstract: De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

PubMed: 28953867
DOI: 10.1038/nature23912

Experimental method

X-RAY DIFFRACTION (1.799 Å)