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实验室提议开发和测试一个水反应平衡的热力学框架，将溶剂视为共反应。新方法是由于以下事实激发了液态水中氢键的数量和方向，并且在溶质附近发生了变化，并且由于水结构中的重排伴随传统反应物向产物的转化，因此应包括在系统的总自由能变化中。尽管对于涉及形成和/或破裂共价键的化学反应的溶剂贡献可能可以忽略不计，但水结构的变化可能在结合平衡和构象平衡中起主要作用。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，包括蛋白质折叠和多核酸，DNA和RNA的结构。 将实施生物物理技术的结合，包括两种类型的量热量实验，以测试新框架的有效性。将测量和列出大量水的焓和熵值，以用于许多感兴趣的解决方案，包括中性盐，渗透剂，混合物和拥挤剂。将新框架应用于模型化合物的溶解度，应导致对大分子结构中水合力的定量评估。 这项研究提供了一种理解溶质对生物平衡的影响的替代观点，这种观点可能比当前模型更直观，更广泛地适用。此外，这项研究可能会产生有关分子识别和药物设计的新见解。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的逼真的力场中非常有用，这是对生物过程的计算机模拟的重要考虑因素。 公共卫生相关性：这项研究旨在量化水分子参与一些特定反应，这些反应可能被视为活细胞中许多关键分子事件的模型。基本发现将对所有分子和细胞生物学有影响，因此，对所有涉及人类健康和疾病的研究。