Biophysical Reviews

, Volume 11, Issue 2, pp 209–225 | Cite as

Ionic liquids and protein folding—old tricks for new solvents

  • Ryota Wakayama
  • Susumu Uchiyama
  • Damien HallEmail author


One important aspect of the green chemistry revolution has been the use of ionic liquids as the solvent in liquid-phase enzymatic catalysis. An essential requirement for protein enzyme function is the correct folding of the polypeptide chain into its functional “native” state. Quantitative assessment of protein structure may be carried out either empirically, or by using model-based characterization procedures, in which the parameters are defined in terms of a standard reference state. In this short note, we briefly outline the nature of the parameters associated with different empirical and model-based characterization procedures and point out factors which affect their interpretation when using a base solvent different from water. This review principally describes arguments developed by Wakayama et al., Protein Solubility and Amorphous Aggregation: From Academic Research to Applications in Drug Discovery and Bioindustry, 2019, edited by Y. Kuroda and F. Arisaka; CMC Publishing House. Sections of that work are translated from the original Japanese and republished here with the full permission of CMC Publishing Corporation.


Protein folding Ionic liquids Data reduction Thermodynamic characterization 



DH acknowledges Dr. Nicholas Kanizaj, Dr. Bradley Stevenson, and Dr. Christoph Nitsche from the Research School of Chemistry at the ANU for helpful comments on an earlier version of this manuscript and Dr. Allen Minton, of the NIH, for conversations relating to the derivation of the Gibbs-Helmholtz equation.

Compliance with ethical standards

Funding information

The work of DH was jointly supported by funds and resources associated with an Australian National University (ANU) Senior Research Fellowship, a Guest Associate Professor position at the Institute for Protein Research, Osaka University and a short term fellowship at the Laboratory of Biochemistry and Genetics of the NIH (NIDDK) in August of 2018. The receipt of a TOBITATE exchange program grant funded a 1-year exchange for RW to ANU. TOBITATE was funded by the Japan National Exchange Program part of the Ministry of Education, Culture Science and Technology (MEXT) of Japan.

Conflict of interest

Ryota Wakayama declares that he has no conflict of interest. Susumu Uchiyama declares that he has no conflict of interest. Damien Hall declares that he has no conflict 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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© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biotechnology, Graduate School of EngineeringOsaka UniversityOsakaJapan
  2. 2.Institute for Protein ResearchOsaka UniversityOsakaJapan

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