"Probing the Hydrogen Bonding Properties of the Protein-Water Interface and its Effects on Protein Stability, Function and Dynamics"

所有蛋白质的共同成分是它们的水溶剂壳。可以说，在蛋白质结构和动力学中最重要的角色是水溶剂分子。然而(即使经过了40多年的研究)，水的作用仍然是所有人中最不了解的。当蛋白质溶解在水溶液中时，它将溶剂分子分成两组：散装水分子和构成蛋白质水合壳的分子。早期的蛋白质水合实验表明，蛋白质的结构和功能需要最小的水合作用，这表明了蛋白质水合球体的关键作用。我的团队目前的研究重点是了解溶剂水分子--特别是那些位于蛋白质水合球体中的分子--在确保蛋白质承担正确的折叠和功能方面所起的作用。要更好地了解水合球体的作用，一个非常有效的方法是用被称为渗透剂的化学试剂扰乱这些水的性质，然后确定这种扰动对蛋白质结构和功能的影响。渗透分子是生物体在高度变性的条件下稳定蛋白质的分子。TMAO(三甲胺N-氧化物)等分子通过抵消海洋生物细胞中高浓度尿素的影响来稳定蛋白质，而甜菜碱、山梨醇和肌醇等物种在肾脏细胞中也发挥着类似的作用。虽然渗透剂是蛋白质折叠状态的强稳定剂，但其对蛋白质的作用机制在分子水平上仍不完全清楚。然而，大多数解释一致认为，渗透分子诱导稳定的起源在于这些分子对水化球体的影响。了解渗透压作用的机制将为我们提供一个框架，用于研究水合水在拥挤的细胞环境中的作用，这是我们探索了解水在真实细胞的生物化学中所起作用的长期目标。

The common component of all proteins is their aqueous solvent shell. Arguably, the most important role in protein structure and dynamics is played by the water solvent molecules. However (even after more than four decades of research), it is the role of water that remains the least understood of all. When a protein is dissolved in aqueous solvent it divides the solvent molecules into two groups: bulk water molecules and the molecules that constitute the protein hydration shell. Early experiments in protein hydration demonstrate that minimal hydration is required for protein structure and function pointing to the crucial role of the protein hydration sphere. The current research focus of my group is on understanding the role that solvent water molecules -especially those molecules located in the protein hydration sphere, play in ensuring proteins assume the correct fold and function. An extremely powerful method to better understand the role of the hydration sphere is to perturb the properties of these waters with chemical agents called osmolytes and subsequently determine the effect of this perturbation on the protein structure and function. Osmolytes are molecules produced by living organisms that stabilize proteins under highly denaturing conditions. Molecules such as TMAO (Trimethylamine N-oxide) stabilize the proteins by counteracting the effects of high concentrations of urea in the cells of marine organisms, while species such as betaine, sorbitol and inositol play a similar role in kidney cells. Although it has been known for a long time that osmolytes are strong stabilizers of the protein folded state, their mechanism of action on proteins is still not fully understood at the molecular level. However, most interpretations agree that the origin of osmolyte induced stabilization lies in the changes that these molecules effect on the hydration sphere. Understanding the mechanism by which osmolytes work will provide us with a framework for investigating the role of hydration water in crowded cellular environments, a long-term goal in our quest in understanding the role water plays in the biochemistry of real cells.