Distinct and Nonadditive Effects of Urea and Guanidinium Chloride on Peptide Solvation
Distinct and Nonadditive Effects of Urea and Guanidinium Chloride on Peptide Solvation
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DOI：
10.1021/acs.jpclett.9b03004
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发表时间：
2019-12-05
影响因子：
5.7
通讯作者：
Shea, Joan-Emma
中科院分区：
文献类型：
--
作者：
Ganguly, Pritam;Shea, Joan-Emma
使用增强采样复制交换完全原子分子动力学模拟，我们表明，单独地，尿素和氯化胍（GdmCl）变性的Trpcage蛋白质，但值得注意的是，螺旋段（1）NLYIQWL（7）的蛋白质是稳定的混合变性剂溶液。GdmCl通过直接和间接作用的组合诱导蛋白质变性，所述直接和间接作用涉及蛋白质的脱水和稳定盐桥的去稳定化。相反，尿素通过有利的蛋白质-尿素优先相互作用使蛋白质变性，尿素对蛋白质周围的水结构具有肽特异性间接作用。在Trpcage的螺旋区段的情况下，脲通过将水分子从肽侧链重组到肽主链来“过溶剂化”肽主链。GdmCl诱导的肽脱水和尿素诱导的溶剂化结构变化之间的复杂的非加性热力学平衡触发部分抵消尿素变性和稳定的螺旋。
Using enhanced-sampling replica exchange fully atomistic molecular dynamics simulations, we show that, individually, urea and guanidinium chloride (GdmCl) denature the Trpcage protein, but remarkably, the helical segment (1)NLYIQWL(7) of the protein is stabilized in mixed denaturant solutions. GdmCl induces protein denaturation via a combination of direct and indirect effects involving dehydration of the protein and destabilization of stabilizing salt bridges. In contrast, urea denatures the protein through favorable protein-urea preferential interactions, with peptide-specific indirect effects of urea on the water structure around the protein. In the case of the helical segment of Trpcage, urea "oversolvates" the peptide backbone by reorganizing water molecules from the peptide side chains to the peptide backbone. An intricate nonadditive thermodynamic balance between GdmCl-induced dehydration of the peptide and the urea-induced changes in solvation structure triggers partial counteraction to urea denaturation and stabilization of the helix.