Biophysical Reviews

, Volume 10, Issue 2, pp 391–410 | Cite as

Hierarchical design of artificial proteins and complexes toward synthetic structural biology

  • Ryoichi Arai


In multiscale structural biology, synthetic approaches are important to demonstrate biophysical principles and mechanisms underlying the structure, function, and action of bio-nanomachines. A central goal of “synthetic structural biology” is the design and construction of artificial proteins and protein complexes as desired. In this paper, I review recent remarkable progress of an array of approaches for hierarchical design of artificial proteins and complexes that signpost the path forward toward synthetic structural biology as an emerging interdisciplinary field. Topics covered include combinatorial and protein-engineering approaches for directed evolution of artificial binding proteins and membrane proteins, binary code strategy for structural and functional de novo proteins, protein nanobuilding block strategy for constructing nano-architectures, protein–metal–organic frameworks for 3D protein complex crystals, and rational and computational approaches for design/creation of artificial proteins and complexes, novel protein folds, ideal/optimized protein structures, novel binding proteins for targeted therapeutics, and self-assembling nanomaterials. Protein designers and engineers look toward a bright future in synthetic structural biology for the next generation of biophysics and biotechnology.


Artificial protein and complex Combinatorial library Computational design Directed evolution Hierarchical design Protein engineering 



I thank all colleagues and collaborators, especially, Dr. Naoya Kobayashi and Dr. Nobuyasu Koga at Institute for Molecular Science (IMS), Prof. Michael H. Hecht at Princeton University, Dr. Shinya Honda at Advanced Industrial Science and Technology, and Dr. Tomoaki Matsuura at Osaka University for their help and valuable discussion. I apologize to the protein designers and protein engineers whose works I was unable to acknowledge due to space and scope limitations. This work was supported by JSPS KAKENHI Grant Numbers JP16K05841 and JP16H00761 (an Innovative Area, “Dynamical Ordering and Integrated Functions”), and Joint Research by IMS.

Compliance with ethical standards

Conflict of interest

Ryoichi Arai declares that he has no conflicts of interest.

Ethical approval

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


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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 Biology, Faculty of Textile Science and TechnologyShinshu UniversityUedaJapan
  2. 2.Department of Supramolecular Complexes, Research Center for Fungal and Microbial DynamismShinshu UniversityMinamiminowaJapan
  3. 3.Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge ResearchShinshu UniversityMatsumotoJapan
  4. 4.Division of Structural and Synthetic BiologyRIKEN Center for Life Science TechnologiesYokohamaJapan

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