preferential solvation: Osmolyte solvation of proteins, aminoacids, and peptides
preferential solvation: Osmolyte solvation of proteins, aminoacids, and peptides
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DOI：
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发表时间：
2008
影响因子：
8.2
通讯作者：
M. Auton;D. W. Bolen;J. Rösgen
中科院分区：
文献类型：
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作者：
M. Auton;D. W. Bolen;J. Rösgen
蛋白质的稳定性和溶解度很大程度上取决于渗透剂的存在，因为蛋白质倾向于被水或渗透剂溶剂化。传统上认为只能测量这种相对偏好，并且水和渗透剂的单独溶剂化作用是无法测量的。然而，可以使用 Kirkwood-Buff 理论分别确定水合和渗透剂溶剂化（渗透），并且这一事实最近已被一些研究人员利用。在这里，我们对蛋白质上的每个表面基团如何促进整体水合和渗透作用进行了热力学评估。我们的分析基于模型化合物的转移自由能测量，先前已证明这些模型化合物可以非常成功地预测渗透剂依赖性蛋白质稳定性。当与 Kirkwood-Buff 理论相结合时，传递模型提供了肽单元、氨基酸以及渗透剂存在下蛋白质折叠/解折叠平衡的空间分辨溶剂化模式。我们发现对蛋白质侧链的主要溶剂化作用源自渗透剂，并且水合作用主要取决于侧链的大小。肽骨架单元在不同的渗透剂溶液中表现出更加可变的水合作用。有趣的是，蔗糖的存在导致糖和水在肽基团附近同时积累，这是由于糖的积累少于水的积累，这是一种净优先排斥。只有变性渗透剂尿素遵循经典的溶剂交换机制，其中与肽单元的优先相互作用排除了水。
Protein stability and solubility depend strongly on the presence of osmolytes, because of the protein preference to be solvated by either water or osmolyte. It has traditionally been assumed that only this relative preference can be measured, and that the individual solvation contributions of water and osmolyte are inaccessible. However, it is possible to determine hydration and osmolyte solvation (osmolation) separately using Kirkwood-Buff theory, and this fact has recently been utilized by several researchers. Here, we provide a thermodynamic assessment of how each surface group on proteins contributes to the overall hydration and osmolation. Our analysis is based on transfer free energy measurements with model-compounds that were previously demonstrated to allow for a very successful prediction of osmolyte-dependent protein stability. When combined with Kirkwood-Buff theory, the Transfer Model provides a space-resolved solvation pattern of the peptide unit, amino acids, and the folding/unfolding equilibrium of proteins in the presence of osmolytes. We find that the major solvation effects on protein side-chains originate from the osmolytes, and that the hydration mostly depends on the size of the side-chain. The peptide backbone unit displays a much more variable hydration in the different osmolyte solutions. Interestingly, the presence of sucrose leads to simultaneous accumulation of both the sugar and water in the vicinity of peptide groups, resulting from a saccharide accumulation that is less than the accumulation of water, a net preferential exclusion. Only the denaturing osmolyte, urea, obeys the classical solvent exchange mechanism in which the preferential interaction with the peptide unit excludes water.