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

Sota Yagi, Satoshi Akanuma, Akihiko Yamagishi*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)


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
Issue number2
Publication statusPublished - 2018 Apr 1


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

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Creation of artificial protein–protein interactions using α-helices as interfaces'. Together they form a unique fingerprint.

Cite this