Statistical thermodynamics of protein stability in mixed aqueous solutions

生物分子（如蛋白质，DNA，膜）在大多数情况下被水分子包围。水分子在其功能中起着至关重要的作用。当配体与蛋白质结合时，水分子必须从结合位点排出，这通常是结合反应的瓶颈。当蛋白质折叠时，疏水（非极性）侧链的脱水是主要驱动力之一。因此，计算释放的水分子的数量对于理解这些过程的机制至关重要。最近，我已经开发了一个严格的统计热力学理论在混合溶剂中的生物分子溶剂化，并表明，这些数字可以从实验中获得，通过结合这些过程中的体积变化与数据的结构变化。根据这些数字，我将计算出生物分子附近的水的结构。这将有助于了解水分子如何促进生化反应。此外，存在的共溶剂，如盐，渗透剂和其他生物分子，影响生物分子的结合和折叠。我最近表明，在这些过程中所涉及的水和共溶剂的数量可以通过结合体积变化，共溶剂引起的平衡移动，和结构信息的数据来计算。这一理论被应用于解释蛋白质如何被渗透剂保护免受变性应力，蛋白质-配体结合如何受到代谢物和盐分子的影响，以及其他生物分子的存在如何影响蛋白质的稳定性。

Biomolecules (such as proteins, DNAs, membranes) are surrounded in most cases by water molecules. Water molecules play crucial role in their function. When ligands bind proteins, water molecules must be expelled from the binding sites, and this is often a bottleneck of binding reactions. When a protein folds, dehydration of hydrophobic (non-polar) side chains is one of the major driving forces. Therefore, counting the number of water molecules released is crucial to the understanding of the mechanism of these processes. Recently, I have developed a rigorous statistical thermodynamic theory on biomolecular solvation in mixed solvents, and have shown that these numbers can be obtained from experiments, by combining volume changes upon these processes with data on structural changes. Based upon these numbers, I will characterise the structure of water in the close vicinity of biomolecules. This will help understand how water molecules contribute to the biochemical reactions. In addition, the presence of cosolvents, such as salts, osmolytes and other biomolecules, affect the binding and folding of biomolecules. I have shown recently that the numbers of water and cosolvents involved in these processes can be counted by combining the data on volume change, cosolvent-induced shift of equilibrium, and structural information. This theory is applied to explain how proteins are protected from denaturing stresses by osmolytes, how protein-ligand binding is affected by metabolite and salt molecules, and how the presence of other biomolecules affect the stability of proteins.