A new interpretation of solute effects on biological equilibria

溶质对生物平衡影响的新解释

• 批准号: 8206624
• 负责人: DARYL K EGGERS
• 金额: $ 10.65万
• 依托单位: SAN JOSE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206624
• 关键词: Acids; Binding; Biochemistry; Biological; Biological Process; CCL7 gene; Calorimetry; Cells; Chemicals; Computer Simulation; Crowding; DNA; DNA Sequence Rearrangement; Data; Development; Disease; Distant; Drug Design; Entropy; Environment; Equation; Equilibrium; Event; Free Energy; Goals; Grant; Health; Human; Hydration status; Hydrogen Bonding; Ions; Laboratories; Lead; Life; Liquid substance; Measurement; Measures; Membrane Lipids; Mentors; Methods; Mind; Minority; Modeling; Molecular; Molecular Structure; Molecular and Cellular Biology; Outcome; Output; Paper; Play; Protein Conformation; Proteins; Publications; RNA; Reaction; Research; Role; Salts; Scientist; Series; Solubility; Solutions; Solvents; Structure; Students; System; Techniques; Testing; Textbooks; Thermodynamics; Titrations; United States National Institutes of Health; Universities; Water; Work; aqueous; base; bulk phase water; chemical reaction; covalent bond; driving force; enthalpy; insight; interest; macromolecule; meetings; molecular recognition; novel strategies; programs; protein folding; research study; skills; solute; success; symposium

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.

描述（由申请人提供）：Eggers 实验室建议开发和测试将溶剂视为共反应物的水反应平衡的热力学框架。新方法的动机是液态水中氢键的数量和方向在溶质附近发生改变，并且水结构的重排（伴随传统反应物转化为产物）应该包括在内系统总自由能变化。尽管溶剂的贡献对于涉及共价键形成和/或断裂的化学反应可以忽略不计，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，这项研究有望增强我们对水在许多重要生物反应中的作用的理解，包括蛋白质折叠以及多核酸、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。对于许多感兴趣的溶液，包括中性盐、渗透剂、离液剂和拥挤剂，将测量大量水的焓和熵值并制成表格。将新框架应用于模型化合物的溶解度应该可以定量评估大分子结构中的水合力。 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、更广泛适用。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对于计算科学家在界面处开发水的真实力场可能非常有用，这是计算机模拟生物过程的重要考虑因素。 公共健康相关性：这项研究旨在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，从而影响所有涉及人类健康和疾病的研究。