Protein design

Protein design (or protein engineering) is a technique by which proteins with enhanced or novel functional properties are created. Proteins can be engineered by rational design, which typically uses computational tools to identify useful mutations, or by directed evolution, which uses random mutagenesis coupled with a selection process to identify desired variants.

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Latest Research and Reviews

  • Research |

    The ‘jGCaMP7’ sensors are four genetically encoded calcium indicators with better sensitivity than state-of-the-art GCaMP6 and specifically improved for applications such as neuropil or wide-field imaging. The sensors are validated in vivo in both flies and mice.

    • Hod Dana
    • , Yi Sun
    • , Boaz Mohar
    • , Brad K. Hulse
    • , Aaron M. Kerlin
    • , Jeremy P. Hasseman
    • , Getahun Tsegaye
    • , Arthur Tsang
    • , Allan Wong
    • , Ronak Patel
    • , John J. Macklin
    • , Yang Chen
    • , Arthur Konnerth
    • , Vivek Jayaraman
    • , Loren L. Looger
    • , Eric R. Schreiter
    • , Karel Svoboda
    •  & Douglas S. Kim
  • Research |

    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
    • , Tamir Husain
    • , Alex Ford
    • , Daniel-Adriano Silva
    • , Matthew J. Bick
    • , Aaron Bauer
    • , Gaohua Liu
    • , Yojiro Ishida
    • , Alexander Boykov
    • , Roger D. Estep
    • , Susan Kleinfelter
    • , Toke Nørgård-Solano
    • , Linda Wei
    • , Foldit Players
    • , Gaetano T. Montelione
    • , Frank DiMaio
    • , Zoran Popović
    • , Firas Khatib
    • , Seth Cooper
    •  & David Baker
    Nature, 1-5
  • Research |

    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
    • , Amina Frese
    • , Rebecca Crawshaw
    • , Mary Ortmayer
    • , Mark Dunstan
    • , Colin Levy
    •  & Anthony P. Green
    Nature 570, 219-223
  • Research |

    Rewiring of bacterial two-component systems (TCSs) was achieved by DNA-binding domain swapping of the two largest response regulator families, which enables cross-species porting and provides a tool for identifying ligands for uncharacterized TCSs.

    • Sebastian R. Schmidl
    • , Felix Ekness
    • , Katri Sofjan
    • , Kristina N.-M. Daeffler
    • , Kathryn R. Brink
    • , Brian P. Landry
    • , Karl P. Gerhardt
    • , Nikola Dyulgyarov
    • , Ravi U. Sheth
    •  & Jeffrey J. Tabor
  • Research |

    Deep neural networks are a powerful tool for predicting protein function, but identifying the specific parts of a protein sequence that are relevant to its functions remains a challenge. An occlusion-based sensitivity technique helps interpret these deep neural networks, and can guide protein engineering by locating functionally relevant protein positions.

    • Julius Upmeier zu Belzen
    • , Thore Bürgel
    • , Stefan Holderbach
    • , Felix Bubeck
    • , Lukas Adam
    • , Catharina Gandor
    • , Marita Klein
    • , Jan Mathony
    • , Pauline Pfuderer
    • , Lukas Platz
    • , Moritz Przybilla
    • , Max Schwendemann
    • , Daniel Heid
    • , Mareike Daniela Hoffmann
    • , Michael Jendrusch
    • , Carolin Schmelas
    • , Max Waldhauer
    • , Irina Lehmann
    • , Dominik Niopek
    •  & Roland Eils

News and Comment

  • News and Views |

    Nature harnesses fractal geometry to create structures with unusual surface-to-volume ratios. Now, a new design approach enables the reversible assembly of functional enzymes into arboreal patterns with fractal geometry.

    • Iris D. Young
    •  & James S. Fraser
  • News and Views |

    High-yield production of a functionally active mimic of particulate methane monooxygenase in Escherichia coli has been presented. Investigation of its catalytic mode clarifies the role of duroquinol in biomimetic methanol production.

    • Sunney I. Chan
    •  & Steve S.-F Yu
    Nature Catalysis 2, 286-287
  • News and Views |

    A new method introduces ubiquitin or ubiquitin-like proteins at specific sites in any protein without the requirement of the cellular ubiquitylation machinery. This will help decipher the code by which these modifications control cellular processes.

    • Amit Kumar Singh Gautam
    •  & Andreas Matouschek
  • News and Views |

    Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron flux.

    • Michaela TerAvest
  • News and Views |

    Two protein circuit systems, split-protease-cleavable orthogonal coiled-coil logic (SPOC logic) and circuits of hacked orthogonal modular proteases (CHOMP), have been developed to permit rapid and logic function-based control of mammalian cellular signaling.

    • Yiqian Wu
    •  & Yingxiao Wang