Biophysical Reviews

, Volume 10, Issue 2, pp 411–420 | Cite as

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

Review

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.

Keywords

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

Notes

Acknowledgements

The work was supported by JSPS KAKENHI Grant Number 16K14494 to S.A. and by MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1512002), 2015–2017 to A.Y.

Compliance with ethical standards

Conflict of interest

Sota Yagi declares that he has no conflicts of interest. Satoshi Akanuma declares that he has no conflicts of interest. Akihiko Yamagishi declares that he has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Applied Life SciencesTokyo University of Pharmacy and Life SciencesTokyoJapan
  2. 2.Faculty of Human SciencesWaseda UniversitySaitamaJapan

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