Department of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan.
Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
J Phys Chem B. 2022 Apr 7;126(13):2466-2475. doi: 10.1021/acs.jpcb.1c10634. Epub 2022 Mar 29.
There is a long, ongoing debate on how small molecules (osmolytes) affect the stability of proteins. The present study found that change in collective rotational dynamics of water in osmolyte solutions likely has a dominant effect on protein denaturation. According to THz spectroscopy analysis, osmolytes that stabilize proteins are accompanied by bound hydration water with slow dynamics, while the collective rotational dynamics of water is accelerated in the case of denaturant osmolytes. Among 15 osmolytes studied here, there is a good correlation between the change in mobility in terms of water rotational dynamics and the denaturation temperature of ribonuclease A. The changes in water dynamics due to osmolytes can be regarded as a pseudo-temperature-change, which agrees well with the change in protein denaturation temperature. These results indicate that the molecular dynamics of water around the protein is a key factor for protein denaturation.
关于小分子（渗透物）如何影响蛋白质稳定性，一直存在着长期的争论。本研究发现，渗透物溶液中水分子的集体旋转动力学的变化可能对蛋白质变性有主导作用。根据太赫兹光谱分析，稳定蛋白质的渗透物伴随着结合水的慢动力学，而在变性渗透物的情况下，水的集体旋转动力学则被加速。在研究的 15 种渗透物中，水旋转动力学的流动性变化与核糖核酸酶 A 的变性温度之间存在很好的相关性。渗透物引起的水动力学变化可以看作是一种伪温度变化，与蛋白质变性温度的变化非常吻合。这些结果表明，蛋白质周围水分子的分子动力学是蛋白质变性的关键因素。
