A new interpretation of solute effects on biological equilibria

描述(由申请人提供)：埃格斯实验室建议开发和测试将溶剂作为共反应物的水反应平衡的热力学框架。这一新方法是基于这样一个事实，即液态水中氢键的数目和取向在溶质附近发生变化，以及伴随着传统反应物向产物转化的水结构的重排应计入体系的总自由能变化中。尽管在涉及共价键的形成和/或断裂的化学反应中，溶剂的贡献可以忽略不计，但水结构的变化可能在结合平衡和构象平衡中起主导作用。因此，这项研究有望加深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。将实施生物物理技术的组合，包括两种类型的量热实验，以测试新框架的有效性。将测量散装水的热值和熵值，并将其列为许多感兴趣的溶液的列表，包括中性盐、渗透压、共沸物和聚集剂。将新的框架应用于模型化合物的溶解度，应该导致对大分子结构中的水合力进行定量评估。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目前的模型更直观、更适用。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对计算科学家在开发界面上的水的真实力场方面非常有用，这是计算机模拟生物过程的重要考虑因素。 与公共健康相关：这项研究旨在量化水分子在几个特定反应中的参与，这些反应可能被视为发生在活细胞中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.