A new interpretation of solute effects on biological equilibria

描述（由申请人提供）：Eggers实验室建议开发和测试将溶剂作为共反应物的含水反应平衡的热力学框架。这种新方法的动机是，在液态水中的氢键的数量和方向改变附近的溶质，并在水结构的重排，这伴随着传统的反应物的产品的转换，应包括在系统的总自由能变化的事实。虽然溶剂的贡献可以忽略不计的化学反应，涉及形成和/或共价键的断裂，水结构的变化可能发挥主导作用的结合平衡和构象平衡。因此，这项研究有望提高我们对水在许多重要生物反应中的作用的理解，包括蛋白质折叠和多核酸，DNA和RNA的结构。 生物物理技术的组合，包括两种类型的量热实验，将被实施，以测试新框架的有效性。大量水的焓值和熵值将被测量和制表为许多感兴趣的解决方案，包括中性盐，渗透剂，离液剂，和拥挤剂。新的框架模型化合物的溶解度的应用，应导致在大分子结构中的水合力的定量评估。 这项研究为理解溶质对生物平衡的影响提供了另一种观点，这种观点可能被认为比现有模型更直观，适用范围更广。此外，这项研究可能会对分子识别和药物设计产生新的见解。从这项工作中获得的实验数据可能是非常有用的计算科学家在开发现实力场的水在接口，一个重要的考虑因素，计算机模拟生物过程。 公共卫生相关性：这项研究的目的是量化水分子在一些特定反应中的参与，这些反应可以被视为活细胞中发生的许多关键分子事件的模型。这些基本发现将对所有分子和细胞生物学产生影响，因此也将对所有涉及人类健康和疾病的研究产生影响。

DESCRIPTION (provided by applicant): The Eggers laboratory proposes to develop and test a thermodynamic framework for aqueous reaction equilibria that treats the solvent as a co-reactant. The new approach is motivated by the fact that the numbers and orientations of hydrogen bonds in liquid water are altered near a solute, and by the fact that the rearrangement in water structure, which accompanies the conversion of the traditional reactants to products, should be included in the total free energy change of the system. Although the solvent contribution may be negligible for chemical reactions involving formation and/or breakage of covalent bonds, changes in water structure may play a dominant role in binding equilibria and conformational equilibria. Consequently, this research is expected to enhance our understanding of the role of water in many important biological reactions, including protein folding and the structure of the polynucleic acids, DNA and RNA. A combination of biophysical techniques, including two types of calorimetry experiments, will be implemented to test the validity of the new framework. Enthalpy and entropy values of bulk water will be measured and tabulated for many solutions of interest, including neutral salts, osmolytes, chaotropes, and crowding agents. Application of the new framework to the solubility of model compounds should lead to a quantitative assessment of hydration forces in macromolecular structure. This research provides an alternative view for understanding the effects of solutes on biological equilibria, a view that may be deemed as more intuitive and more widely applicable than current models. In addition, this research may yield new insights into molecular recognition and drug design. The experimental data obtained from this work may be extremely useful to computational scientists in developing realistic force fields for water at interfaces, an important consideration for computer simulations of biological processes. PUBLIC HEALTH RELEVANCE: This research aims to quantify the participation of water molecules in a few specific reactions that may be viewed as models for many of the key molecular events that occur in living cells. The basic findings will have implications for all of molecular and cellular biology, and, therefore, for all research involving human health and disease.