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Updated: Mar 14, 2026

How to Stabilize Protein: Stability Screens for Thermal Shift Assays and Nano Differential Scanning Fluorimetry in the Virus-X Project
Published on: February 11, 2019
Protein remains stable at unusually high temperatures when solvated in aqueous mixtures of amino acid based ionic
Guillaume Chevrot1, Eudes Eterno Fileti2, Vitaly V Chaban3
1Department of Physics, Chemistry and Pharmacy, MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark.
Abstract:
Using molecular dynamics simulations, we investigated the thermal stability and real-time denaturation of a model mini-protein in four solvents: (1) water, (2) 1-ethyl-3-methylimidazolium alaninate [EMIM][ALA] (5 mol% in water), (3) methioninate [EMIM][MET] (5 mol% in water), and (4) tryptophanate [EMIM][TRP] (5 mol% in water). Upon analyzing the radius of gyration, the solvent-accessible surface area, root-mean-squared deviations, and inter- and intramolecular hydrogen bonds, we found that the mini-protein remains stable at 30-40 K higher temperatures in aqueous amino acid based ionic liquids (AAILs) than in water. This thermal stability was correlated with the thermodynamics and shear viscosity of the AAIL-containing mixtures. These results suggest that AAILs are generally favorable for protein conservation. Graphical Abstract Conformation of the [TRP]-cage mini-protein in an aqueous amino acid based ionic liquid (AAIL).
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