Influence of osmolytes on densities, solubilities, osmotic pressures and reaction kinetics in high-pressure biological systems

渗透剂对高压生物系统中的密度、溶解度、渗透压和反应动力学的影响

• 批准号: 323941372
• 负责人: Professorin Dr. Gabriele Sadowski
• 金额: --
• 依托单位: Lehrstuhl für Thermodynamik (TH)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323941372?language=en
• 关键词: Influence; osmolytes; densities; solubilities; osmotic

This project studies the influence of osmolytes on the thermodynamic properties of high-pressure biomolecule solutions. Properties of interest are density, osmotic coefficients/osmotic pressures, and solubilities as well as activity coefficients of biomolecules in aqueous solutions.These thermodynamic properties at high pressure will be predicted using the thermodynamic model PC-SAFT (Perturbed-Chain Statistical Associating Fluid Theory) which will be parametrized only using experimental data of densities (measured at pressures up to 500 bar) and osmotic coefficients of biomolecules solutions in the absence and presence of osmolytes. Measured densities at pressures up to 500 bar will be used as reference for density measurements in SP2 and in turn, the latter will be used to validate the densities predicted here for pressures up to 5,000 bar. The PC-SAFT predictions will also be validated via high-pressure solubility data taken from the literature.The so-validated predictions of thermodynamic properties will very well contribute to the overall aims the DFG Research Unit: the investigation and understanding of pressure effects in biological systems and the combined effects of pressure and osmolytes on thermodynamic properties and reaction kinetics.PC-SAFT predictions will allow for reliable predictions of densities and osmotic pressures as function of osmolyte concentration and of hydrostatic pressure. This information will serve for validation of the force fields developed in project SP 7 for molecular dynamic simulations in biomolecule/osmolyte solutions.Using PC-SAFT predictions it will moreover be possible to differentiate the effects of high pressure and osmolytes on thermodynamic properties of biological solutions. Moreover, urea will be investigated as non-osmolyte to further understand the specific effects of osmolytes under high pressure.For the first time, PC-SAFT predicted reactant activity coefficients at high pressure in the absence or presence of osmolytes will be used to model the reaction kinetics of a biological reaction performed at high pressure. This will allow differentiating the effect of pressure/osmolytes on the enzyme (investigated in SP 9) from that on the reactants activity coefficients (which are so far usually neglected). This will open up completely new insights into the influence of pressure/osmolytes on reaction kinetics.

本项目研究渗透物对高压生物分子溶液热力学性质的影响。感兴趣的性质是密度、渗透系数/渗透压、水溶性以及生物分子在水溶液中的活度系数。这些高压下的热力学性质将使用热力学模型PC-SAFT（摄动链统计关联流体理论）进行预测，该模型将仅使用密度（在高达500 bar的压力下测量）和生物分子溶液在没有和存在渗透剂的情况下的渗透系数的实验数据进行参数化。在高达500 bar压力下测量的密度将用作SP2中密度测量的参考，而后者将用于验证此处预测的高达5000 bar压力下的密度。PC-SAFT预测也将通过从文献中获取的高压溶解度数据进行验证。对热力学性质的如此验证的预测将非常有助于DFG研究单位的总体目标：研究和理解生物系统中的压力效应，以及压力和渗透物对热力学性质和反应动力学的综合影响。PC-SAFT预测将允许可靠地预测密度和渗透压作为渗透物浓度和静水压力的函数。该信息将用于验证SP 7项目中开发的用于生物分子/渗透溶液分子动力学模拟的力场。此外，利用PC-SAFT预测，还可以区分高压和渗透物对生物溶液热力学性质的影响。此外，尿素将作为非渗透物进行研究，以进一步了解渗透物在高压下的具体作用。PC-SAFT首次预测了在没有或存在渗透物的情况下高压下的反应物活度系数，将用于模拟高压下生物反应的反应动力学。这将区分压力/渗透物对酶的影响（在SP 9中研究）和对反应物活性系数的影响（迄今为止通常被忽略）。这将为压力/渗透物对反应动力学的影响开辟全新的见解。