Creation of artificial protein–protein interactions using α-helices as interfaces

Sota Yagi, Satoshi Akanuma, Akihiko Yamagishi

    Research output: Contribution to journalReview article

    3 Citations (Scopus)

    Abstract

    Designing novel protein–protein interactions (PPIs) with high affinity is a challenging task. Directed evolution, a combination of randomization of the gene for the protein of interest and selection using a display technique, is one of the most powerful tools for producing a protein binder. However, the selected proteins often bind to the target protein at an undesired surface. More problematically, some selected proteins bind to their targets even though they are unfolded. Current state-of-the-art computational design methods have successfully created novel protein binders. These computational methods have optimized the non-covalent interactions at interfaces and thus produced artificial protein complexes. However, to date there are only a limited number of successful examples of computationally designed de novo PPIs. De novo design of coiled-coil proteins has been extensively performed and, therefore, a large amount of knowledge of the sequence–structure relationship of coiled-coil proteins has been accumulated. Taking advantage of this knowledge, de novo design of inter-helical interactions has been used to produce artificial PPIs. Here, we review recent progress in the in silico design and rational design of de novo PPIs and the use of α-helices as interfaces.

    Original languageEnglish
    Pages (from-to)411-420
    Number of pages10
    JournalBiophysical Reviews
    Volume10
    Issue number2
    DOIs
    Publication statusPublished - 2018 Apr 1

    Fingerprint

    Proteins
    Random Allocation
    Computer Simulation

    Keywords

    • Computational design
    • De novo interactions
    • Interface
    • Novel protein binding
    • Protein–protein interactions

    ASJC Scopus subject areas

    • Biophysics
    • Structural Biology
    • Molecular Biology

    Cite this

    Creation of artificial protein–protein interactions using α-helices as interfaces. / Yagi, Sota; Akanuma, Satoshi; Yamagishi, Akihiko.

    In: Biophysical Reviews, Vol. 10, No. 2, 01.04.2018, p. 411-420.

    Research output: Contribution to journalReview article

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