Hallucinating symmetric protein assemblies

B I M Wicky; L F Milles; A Courbet; R J Ragotte; J Dauparas; E Kinfu; S Tipps; R D Kibler; M Baek; F DiMaio; X Li; L Carter; A Kang; H Nguyen; A K Bera; D Baker

doi:10.1126/science.add1964

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Hallucinating symmetric protein assemblies

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Hallucinating symmetric protein assemblies

B I M Wicky, L F Milles, A Courbet, R J Ragotte, J Dauparas, E Kinfu, S Tipps, R D Kibler, M Baek, F DiMaio, …

Science (American Association for the Advancement of Science), Vol.378(6615), pp.56-61

07/10/2022

DOI: https://doi.org/10.1126/science.add1964

PMID: 36108048

Résumé

Biocompatible Materials - chemistry

Cryoelectron Microscopy

Deep Learning

Models, Molecular

Protein Conformation

Protein Engineering - methods

Protein Subunits - chemistry

Deep learning generative approaches provide an opportunity to broadly explore protein structure space beyond the sequences and structures of natural proteins. Here, we use deep network hallucination to generate a wide range of symmetric protein homo-oligomers given only a specification of the number of protomers and the protomer length. Crystal structures of seven designs are very similar to the computational models (median root mean square deviation: 0.6 angstroms), as are three cryo-electron microscopy structures of giant 10-nanometer rings with up to 1550 residues and symmetry; all differ considerably from previously solved structures. Our results highlight the rich diversity of new protein structures that can be generated using deep learning and pave the way for the design of increasingly complex components for nanomachines and biomaterials.

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Détails

Titre: Hallucinating symmetric protein assemblies
Créateurs - sans rôle: B I M Wicky - Institute for Protein Design, University of Washington, Seattle, WA, USA
L F Milles - Institute for Protein Design, University of Washington, Seattle, WA, USA
A Courbet - Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA
R J Ragotte - Institute for Protein Design, University of Washington, Seattle, WA, USA
J Dauparas - Institute for Protein Design, University of Washington, Seattle, WA, USA
E Kinfu - Institute for Protein Design, University of Washington, Seattle, WA, USA
S Tipps - Institute for Protein Design, University of Washington, Seattle, WA, USA
R D Kibler - Institute for Protein Design, University of Washington, Seattle, WA, USA
M Baek - Institute for Protein Design, University of Washington, Seattle, WA, USA
F DiMaio - Institute for Protein Design, University of Washington, Seattle, WA, USA
X Li - Institute for Protein Design, University of Washington, Seattle, WA, USA
L Carter - Institute for Protein Design, University of Washington, Seattle, WA, USA
A Kang - Institute for Protein Design, University of Washington, Seattle, WA, USA
H Nguyen - Institute for Protein Design, University of Washington, Seattle, WA, USA
A K Bera - Institute for Protein Design, University of Washington, Seattle, WA, USA
D Baker - Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA
Détails de publication: Science (American Association for the Advancement of Science), Vol.378(6615), pp.56-61
Note de subvention: P41 GM103533 / NIGMS NIH HHS P41 GM103311 / NIGMS NIH HHS P30 GM124165 / NIGMS NIH HHS Howard Hughes Medical Institute P30 CA015704 / NCI NIH HHS
Identifiants: 99136070309311
Unité académique: Centre de Biologie Structurale - CBS
Langue: English
Type de ressource: Journal article