Ghosh Soumadwip, Dey Souvik, Patel Mahendra, Chakrabarti Rajarshi
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India.
Phys Chem Chem Phys. 2017 Mar 15;19(11):7772-7787. doi: 10.1039/c6cp08842b.
The folding/unfolding equilibrium of proteins in aqueous medium can be altered by adding small organic molecules generally termed as co-solvents. Denaturants such as urea are instrumental in the unfolding of proteins while protecting osmolytes favour the folded ensemble. Recently, room temperature ionic liquids (ILs) have been shown to counteract the deleterious effect of urea on proteins. In this paper, using atomistic molecular dynamics we show that a ternary mixture containing a particular ammonium-based IL, triethylammonium acetate (TEAA), and urea (in 1 : 5 molar ratio) helps a small 15-residue S-peptide analogue regain most of its native structure, whereas a binary aqueous mixture containing a large amount of urea alone completely distorts it. Our simulations show that the denaturant urea directly interacts with the peptide backbone in the binary mixture while for the ternary mixture both urea as well as the IL are preferentially excluded from the peptide surface.
在水性介质中，蛋白质的折叠/去折叠平衡可通过添加通常称为共溶剂的小分子有机化合物来改变。诸如尿素之类的变性剂有助于蛋白质去折叠，而具有保护作用的渗透溶质则有利于蛋白质的折叠状态。最近研究表明，室温离子液体（ILs）能够抵消尿素对蛋白质的有害影响。在本文中，我们利用原子分子动力学表明，含有特定铵基离子液体三乙铵乙酸盐（TEAA）和尿素（摩尔比为1:5）的三元混合物能帮助一个15残基的小S肽类似物恢复其大部分天然结构，而仅含有大量尿素的二元水性混合物则会使其结构完全扭曲。我们的模拟结果表明，在二元混合物中变性剂尿素直接与肽主链相互作用，而在三元混合物中，尿素和离子液体都优先被排除在肽表面之外。
