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.

本课题研究渗透分子对高压生物分子溶液热力学性质的影响。生物分子在水溶液中的密度、渗透系数/渗透压、溶解度和活度系数是重要的性质。高压下的这些热力学性质将使用热力学模型PC-SAFT(微扰链统计缔合流体理论)进行预测，该模型将仅使用生物分子溶液在没有渗透分子和存在渗透分子时的密度(压力高达500bar时测量)和渗透系数的实验数据进行参数化。在压力高达500巴时测得的密度将被用作SP2密度测量的参考，而后者将被用来验证这里预测的压力高达5,000巴的密度。PC-SAFT预测也将通过文献中的高压溶解度数据得到验证。如此验证的热力学性质预测将非常有助于DFG研究单位的总体目标：调查和了解生物系统中的压力效应，以及压力和渗透分子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分子浓度和流体静压的函数。这些信息将用于验证SP7项目中开发的用于生物分子/渗透分子溶液分子动力学模拟的力场。此外，使用PC-SAFT预测将有可能区分高压和渗透分子对生物溶液热力学性质的影响。此外，将尿素作为非渗透分子进行研究，以进一步了解渗透分子在高压下的具体作用。首次使用PC-SAFT预测的在没有或存在渗透分子的情况下高压下的反应物活度系数将用于模拟在高压下进行的生物反应的反应动力学。这将允许区分压力/渗透压对酶的影响(在SP 9中进行了研究)和对反应物活度系数的影响(到目前为止通常被忽略)。这将为研究压力/渗透摩尔分数对反应动力学的影响提供全新的见解。