Protein design articles within Nature

Featured

  • Article
    | Open Access

    Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.

    • Franziska L. Sendker
    • , Yat Kei Lo
    •  & Georg K. A. Hochberg

  • Article
    | Open Access

    Evolution has produced a range of diverse proteins, and now a generative model called Chroma can expand that set by allowing the user to design new proteins and protein complexes with desired properties and functions.

    • John B. Ingraham
    • , Max Baranov
    •  & Gevorg Grigoryan

  • Article
    | Open Access

    Fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks yields a generative model for protein design that achieves outstanding performance on a wide range of protein structure and function design challenges.

    • Joseph L. Watson
    • , David Juergens
    •  & David Baker

  • Article
    | Open Access

    A deep-learning-based strategy is used to design artificial luciferases that catalyse the oxidative chemiluminescence of diphenylterazine with high substrate specificity and catalytic efficiency.

    • Andy Hsien-Wei Yeh
    • , Christoffer Norn
    •  & David Baker

  • Article |

    NMR spectroscopy has been used to guide the directed evolution of myoglobin to a Kemp eliminase with high catalytic efficiency, outlining an approach that is likely to be generally applicable to other enzyme activities.

    • Sagar Bhattacharya
    • , Eleonora G. Margheritis
    •  & Ivan V. Korendovych

  • Article |

    A study demonstrates the rational de novo design of water-soluble assemblies constructed from long 310-helical peptides, and details their characterization by circular dichroism spectroscopy, analytical ultracentrifugation and X-ray crystallography.

    • Prasun Kumar
    • , Neil G. Paterson
    •  & Derek N. Woolfson

  • Article
    | Open Access

    A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

    • Longxing Cao
    • , Brian Coventry
    •  & David Baker

  • Article |

    The trRosetta neural network was used to iteratively optimise model proteins from random 100-amino-acid sequences, resulting in ‘hallucinated’ proteins, which when expressed in bacteria closely resembled the model structures.

    • Ivan Anishchenko
    • , Samuel J. Pellock
    •  & David Baker

  • Article |

    The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.

    • Raoul De Gasparo
    • , Mattia Pedotti
    •  & Luca Varani

  • Article |

    A modular de novo designed biosensor platform consisting of a cage and key molecule is developed, and used to create sensors for seven distinct proteins including the spike protein from SARS-CoV-2 and anti-SARS antibodies.

    • Alfredo Quijano-Rubio
    • , Hsien-Wei Yeh
    •  & David Baker

  • Article |

    An approach for the design of protein pores is demonstrated by the computational design and subsequent experimental expression of both an ion-selective and a large transmembrane pore.

    • Chunfu Xu
    • , Peilong Lu
    •  & David Baker

  • Article |

    A technique for the de novo design of switchable protein systems controlled by induced conformational change is demonstrated for three functional motifs, in vitro and in yeast and mammalian cells.

    • Robert A. Langan
    • , Scott E. Boyken
    •  & David Baker

  • Letter |

    Proteins designed de novo by players of the online protein-folding game Foldit can be expressed in Escherichia coli and adopt the designed structure in solution.

    • Brian Koepnick
    • , Jeff Flatten
    •  & David Baker

  • Letter |

    A hydrolytic enzyme with a non-canonical organocatalytic mechanism was generated by introducing Nδ-methylhistidine into a designed active site using engineered translation components, allowing optimization of enzyme performance using laboratory evolution.

    • Ashleigh J. Burke
    • , Sarah L. Lovelock
    •  & Anthony P. Green

  • Article |

    A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

    • Daniel-Adriano Silva
    • , Shawn Yu
    •  & David Baker

  • Article |

    A massively parallel computational and experimental approach for de novo designing and screening small hyperstable proteins targeting influenza haemagglutinin and botulinum neurotoxin B identifies new therapeutic candidates more robust than traditional antibody therapies.

    • Aaron Chevalier
    • , Daniel-Adriano Silva
    •  & David Baker

  • Letter |

    Introducing a single ‘sticky’ (hydrophobic) amino acid by point mutation into symmetric protein complexes frequently triggers their association into higher-order assemblies, without affecting their native fold and structure.

    • Hector Garcia-Seisdedos
    • , Charly Empereur-Mot
    •  & Emmanuel D. Levy

  • Article |

    Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

    • Gaurav Bhardwaj
    • , Vikram Khipple Mulligan
    •  & David Baker

  • Letter |

    The computational design of an extremely stable icosahedral self-assembling protein nanocage is presented; the icosahedron should be useful for applications ranging from calibrating fluorescence microscopy to drug delivery.

    • Yang Hsia
    • , Jacob B. Bale
    •  & David Baker

  • Letter |

    In this study, 83 proteins containing helix–loop–helix–loop repeats were designed—with sequences unrelated to known repeat proteins—and experimentally characterized; 43 solution X-ray scattering spectra and 15 structures of the designed proteins show that these non-natural repeat proteins have a broad range of curvatures and that their overall structures are in close agreement with design models.

    • TJ Brunette
    • , Fabio Parmeggiani
    •  & David Baker

  • Letter |

    Computational protein design is used to create a protein–DNA co-assembling nanomaterial; by varying the arrangement of protein-binding sites on the double-stranded DNA, a ‘nanowire’ with single-molecule width can be spontaneously formed by mixing the protein and double-stranded DNA building blocks.

    • Yun Mou
    • , Jiun-Yann Yu
    •  & Stephen L. Mayo

  • Article |

    A computational method is reported that can be used to design protein nanomaterials in which two distinct subunits co-assemble into a specific architecture; five 24-subunit cage-like protein nanomaterials are designed, and experiments show that their structures are in close agreement with the computational design models.

    • Neil P. King
    • , Jacob B. Bale
    •  & David Baker

  • Article |

    Computational protein design methods are used to generate new candidates for a human respiratory syncytial virus (RSV) vaccine; artificial protein scaffolds that mimic the structure of a RSV epitope are shown to induce RSV-specific neutralizing antibodies in macaques.

    • Bruno E. Correia
    • , John T. Bates
    •  & William R. Schief

  • Letter |

    A computationally designed enzyme that was evolved to accelerate a chemical reaction 6 × 108-fold approaches the exceptional efficiency of highly optimized natural enzymes and provides valuable lessons for the creation of more sophisticated artificial catalysts.

    • Rebecca Blomberg
    • , Hajo Kries
    •  & Donald Hilvert

  • Letter |

    Computational protein design is used to create a protein that binds the steroid digoxigenin (DIG) with high affinity and selectivity; the computational design methods described here should help to enable the development of a new generation of small molecule receptors for synthetic biology, diagnostics and therapeutics.

    • Christine E. Tinberg
    • , Sagar D. Khare
    •  & David Baker

  • News & Views |

    Some of the principles underlying how amino-acid sequences determine the three-dimensional structures of proteins have been defined. This has enabled a successful approach to designing protein folds from scratch. See Article p.222

    • Birte Höcker

  • News |

    Researchers design proteins from scratch with predictable structures.

    • Jessica Marshall

  • Article |

    Rules that allow the design of strongly funnelled protein folding energy landscapes by relating secondary structure patterns to protein tertiary motifs are used to produce ideal protein structures stabilized by completely consistent local and non-local interactions.

    • Nobuyasu Koga
    • , Rie Tatsumi-Koga
    •  & David Baker

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