Structure and thermodynamics of aqueous urea solutions from ambient to kilobar pressures: From thermodynamic modeling, experiments, and first principles simulations to an accurate force field description
Structure and thermodynamics of aqueous urea solutions from ambient to kilobar pressures: From thermodynamic modeling, experiments, and first principles simulations to an accurate force field description
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DOI：
10.1016/j.bpc.2019.106260
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Horinek, Dominik
中科院分区：
文献类型：
--
作者：
Hoelzl, Christoph;Kibies, Patrick;Horinek, Dominik
基于经典力场的分子模拟是揭示溶液中生物分子复杂行为的有效方法。当除了水和生物分子之外还存在共溶质时，必须考虑弱分子间力的微妙平衡。这对底层力场的质量提出了很高的要求，因此小共质的力场开发仍然是一个活跃的领域。在这里，我们基于实验和理论方法的结合，通过对环境压力和升高的静水压力下的尿素溶液的研究，提出了一种新的尿素力场的发展。环境条件下从头开始分子动力学模拟的实验密度和溶剂化壳特性作为力场优化的目标特性。由于尿素存在于许多海洋生物体内，因此需要严格解决静水压升高的问题：高压下的密度通过高达 500 bar 的振动管密度测定法和高达 5 kbar 的 X 射线吸收来测量。密度由扰动链统计关联流体理论状态方程确定。溶剂化性质由嵌入簇积分方程理论和从头算分子动力学确定。我们的新力场能够在高压下捕获尿素溶液的特性，而无需进一步高压适应，这与必须进行高压适应的三甲胺-N-氧化物不同。
Molecular simulations based on classical force fields are a powerful method for shedding light on the complex behavior of biomolecules in solution. When cosolutes are present in addition to water and biomolecules, subtle balances of weak intermolecular forces have to be accounted for. This imposes high demands on the quality of the underlying force fields, and therefore force field development for small cosolutes is still an active field. Here, we present the development of a new urea force field from studies of urea solutions at ambient and elevated hydrostatic pressures based on a combination of experimental and theoretical approaches. Experimental densities and solvation shell properties from ab initio molecular dynamics simulations at ambient conditions served as the target properties for the force field optimization. Since urea is present in many marine life forms, elevated hydrostatic pressure was rigorously addressed: densities at high pressure were measured by vibrating tube densitometry up to 500 bar and by X-ray absorption up to 5 kbar. Densities were determined by the perturbed-chain statistical associating fluid theory equation of state. Solvation properties were determined by embedded cluster integral equation theory and ab initio molecular dynamics. Our new force field is able to capture the properties of urea solutions at high pressures without further high-pressure adaption, unlike trimethylamine-N-oxide, for which a high-pressure adaption is necessary.