Jójárt Balázs, Viskolcz Béla, Poša Mihalj, Fejer Szilard N
Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, H-6725, Szeged, Hungary.
University of Novi Sad, Faculty of Medicine, Department of Pharmacy, Novi Sad, Serbia.
J Chem Phys. 2014 Apr 14;140(14):144302. doi: 10.1063/1.4869832.
In spite of recent investigations into the potential pharmaceutical importance of bile acids as drug carriers, the structure of bile acid aggregates is largely unknown. Here, we used global optimization techniques to find the lowest energy configurations for clusters composed between 2 and 10 cholate molecules, and evaluated the relative stabilities of the global minima. We found that the energetically most preferred geometries for small aggregates are in fact reverse micellar arrangements, and the classical micellar behaviour (efficient burial of hydrophobic parts) is achieved only in systems containing more than five cholate units. Hydrogen bonding plays a very important part in keeping together the monomers, and among the size range considered, the most stable structure was found to be the decamer, having 17 hydrogen bonds. Molecular dynamics simulations showed that the decamer has the lowest dissociation propensity among the studied aggregation numbers.
尽管最近对胆汁酸作为药物载体的潜在药学重要性进行了研究，但胆汁酸聚集体的结构在很大程度上仍然未知。在此，我们使用全局优化技术来寻找由2至10个胆酸盐分子组成的簇的最低能量构型，并评估全局最小值的相对稳定性。我们发现，小聚集体在能量上最优选的几何形状实际上是反胶束排列，并且仅在含有超过五个胆酸盐单元的系统中才实现经典的胶束行为（疏水部分的有效埋藏）。氢键在使单体聚集在一起方面起着非常重要的作用，在所考虑的尺寸范围内，最稳定的结构是十聚体，具有17个氢键。分子动力学模拟表明，在所研究的聚集数中，十聚体具有最低的解离倾向。
