Department of Biotechnology, BJM School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.
J Phys Chem B. 2021 May 13;125(18):4808-4818. doi: 10.1021/acs.jpcb.1c00586. Epub 2021 Apr 29.
Ionic liquids (ILs) are designer solvents that find wide applications in various areas. Recently, ILs have been shown to induce the refolding of certain proteins that were previously denatured under the treatment of urea. A molecular-level understanding of the counteracting mechanism of ILs on urea-induced protein denaturation remains elusive. In this study, we employ atomistic molecular dynamics simulations to investigate the ternary urea-water-IL solution in comparison to the aqueous urea solution to understand how the presence of ILs can modulate the structure, energetics, and dynamics of urea-water solutions. Our results show that the ions of the IL used, ethylammonium nitrate (EAN), interact strongly with urea and disrupt the urea aggregates that were known to stabilize the unfolded state of the proteins. Results also suggest a disruption in urea-water interaction that releases more free water molecules in solution. We subsequently strengthened these findings by simulating a model peptide in the absence and presence of EAN, which showed broken intact secondary structure in urea solution. Analyses show that these changes were accomplished by the added IL, which enforced a gradual displacement of urea from the peptide surface by water. We propose that the ILs facilitate protein renaturation by breaking down the urea aggregates and increasing the amount of free water molecules around the protein.
离子液体（ILs）是一种设计溶剂，在各个领域都有广泛的应用。最近，已经证明 ILs 可以诱导先前在尿素处理下变性的某些蛋白质的复性。对于 ILs 对尿素诱导的蛋白质变性的拮抗机制的分子水平理解仍然难以捉摸。在这项研究中，我们使用原子分子动力学模拟来研究三元尿素-水-IL 溶液与水合尿素溶液的比较，以了解 ILs 的存在如何调节尿素-水溶液的结构、热力学和动力学。我们的结果表明，所使用的 IL 乙基氯化铵（EAN）的离子与尿素强烈相互作用，并破坏了已知稳定蛋白质展开状态的尿素聚集体。结果还表明，尿素-水相互作用的破坏会释放出更多的游离水分子。随后，我们通过模拟不存在和存在 EAN 的模型肽来加强这些发现，结果表明在尿素溶液中破坏了肽的完整二级结构。分析表明，这些变化是由添加的 IL 完成的，IL 强制水逐渐取代肽表面的尿素。我们提出，IL 通过分解尿素聚集体并增加蛋白质周围游离水分子的数量来促进蛋白质复性。
