Faculty of Applied Computer and Biosciences, University of Applied Sciences Mittweida, Technikumplatz 17, 09648 Mittweida, Germany.
Institute for Organic Chemistry, Technische Universität Bergakademie Freiberg, Leipziger Straße 29, 09599 Freiberg, Germany.
Molecules. 2018 Jul 11;23(7):1690. doi: 10.3390/molecules23071690.
Micro-pollutants such as 17β-Estradiol (E2) have been detected in different water resources and their negative effects on the environment and organisms have been observed. Aptamers are established as a possible detection tool, but the underlying ligand binding is largely unexplored. In this study, a previously described 35-mer E2-specific aptamer was used to analyse the binding characteristics between E2 and the aptamer with a MD simulation in an aqueous medium. Because there is no 3D structure information available for this aptamer, it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside a potential binding area of the predicted aptamer structure, the complex was used for an 25 ns MD simulation, and the interactions were examined for each time step. We identified E2-specific bases within the interior loop of the aptamer and also demonstrated the influence of frequently underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding with aptamer structure in an aqueous solution. The developed workflow allows generating and examining further appealing ligand-aptamer complexes.
微污染物如 17β-雌二醇（E2）已在不同的水资源中被检测到，其对环境和生物的负面影响也已被观察到。适体被确立为一种可能的检测工具，但配体结合的潜在机制在很大程度上仍未被探索。在这项研究中，使用先前描述的 35 个碱基对的 E2 特异性适体，通过在水介质中的 MD 模拟分析 E2 与适体之间的结合特性。由于该适体没有可用的 3D 结构信息，因此使用粗粒度建模方法对其进行建模。将 E2 配体定位在预测适体结构的潜在结合区域内，使用该复合物进行 25ns 的 MD 模拟，并检查每个时间步的相互作用。我们确定了适体内部环中的 E2 特异性碱基，还证明了经常被低估的水介导氢键的影响。该研究有助于理解配体在水溶液中与适体结构结合的行为。所开发的工作流程允许生成和检查进一步有吸引力的配体-适体复合物。
