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Aqueous ionic liquids influence the disulfide bond isoform equilibrium in conotoxin AuIB: a consequence of the Hofmeister effect?

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Abstract

The appearance of several disulfide bond isoforms in multiple cysteine containing venom peptides poses a significant challenge in their synthesis and purification under laboratory conditions. Recent experiments suggest that careful tuning of solvent and temperature conditions can propel the disulfide bond isoform equilibrium in favor of the most potent, native form. Certain aqueous ionic liquids (ILs) have proven significantly useful as solvents for this purpose, while exceptions have also been noted. To elucidate the molecular level origin behind such a preference, we report a detailed explicit solvent replica exchange molecular dynamics study of a conotoxin, AuIB, in pure water and four different aqueous IL solutions (~45–60% v/v). The ILs studied here are comprised of cations like 1-ethyl-3-methyl-imidazolium (Im21+) or 1-butyl-3-methyl-imidazolium (Im41+) coupled with either acetate (OAc−) or chloride (Cl−) as the counter anion. Our simulations unfold interesting features of the conformational spaces sampled by the peptide and its solvation in pure water and aqueous IL solutions. Detailed investigation into populations of the globular disulfide bond isoform of AuIB in aqueous IL solutions reveal distinct trends which might be related to the Hofmeister effect of the cation and anion of the IL and of specific interactions of the aqueous IL solutions with the peptide. In accordance with experimental observations, the aqueous [Im21][OAc] solution is found to promote the highest globular isoform population in AuIB.

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Acknowledgements

DR sincerely acknowledges the encouragement and support received from Professor Mark Maroncelli of the Pennsylvania State University. The authors are thankful to Dr. Debashis Barik, University of Hyderabad, for his kind help in providing computation time. KAS and DR are grateful to the Department of Science & Technology, India (SERB, YSS/2014/000301), for funding. Authors also gratefully acknowledge support from Department of Science and Technology, India, for the FIST grant SR/FST/CSI-240/2012.

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  1. Department of Chemistry, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, Hyderabad, Telangana, 500078, India

    Karuna Anna Sajeevan & Durba Roy

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  1. Karuna Anna Sajeevan
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  2. Durba Roy
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Correspondence to Durba Roy.

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Karuna Anna Sajeevan declares that she has no conflict of interest. Durba Roy declares that she has no conflict of interest.

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This article is part of a Special Issue on ‘Ionic Liquids and Biomolecules’ edited by Antonio Benedetto and Hans-Joachim Galla.

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Sajeevan, K.A., Roy, D. Aqueous ionic liquids influence the disulfide bond isoform equilibrium in conotoxin AuIB: a consequence of the Hofmeister effect?. Biophys Rev 10, 769–780 (2018). https://doi.org/10.1007/s12551-017-0391-2

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