Departamento de Física de Aplicada, Facultade de Física, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
Departamento de Química Orgánica, Center for Research in Biological Chemistry and Molecular Materials, Universidade de Santiago de Compostela, Campus Vida s/n, E-15782 Santiago de Compostela, Spain.
Biomolecules. 2020 Mar 10;10(3):431. doi: 10.3390/biom10030431.
The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulations.
环糊精（CDs）具有篮状几何形状，其空腔能够容纳疏水性基团，因此非常适合许多基础研究和工业应用。大多数已建立的基于 CD 的应用都依赖于反复试验研究，通常忽略了原子水平上的关键信息，而这些信息可以用于设计新产品并优化其使用。计算模拟非常适合填补这一空白，尤其是在 CD 系统的情况下，因为与典型的大分子系统相比，它们的自由度较少。因此，设计和验证用于模拟和分析基于 CD 的系统的有效方法对于推动这一领域的发展至关重要。超分子配合物的行为极大地取决于它们所处的介质，因此需要对溶剂进行详细的表征，以充分理解这些系统。在本工作中，我们使用由两个α-CD 和一个十二烷基硫酸钠分子形成的包合物来测试 GROMOS 和 AMBER 力场的八种不同参数化方法，包括几种旨在增加计算分子动力学模拟轨迹中构象采样的方法。结果表明，该体系对所采用的力场以及水/气界面的存在非常敏感。与先前的实验一致，与 AMBER 的结果相反，使用 GROMOS 对模拟结果的分析表明，复合物很快被吸附到界面上，并且结构周围的水分子在水相中的行为非常奇特，无论是在水相中的 bulk 水溶液中还是在水表面。CD 分子的手性似乎在这种行为中起着重要作用。总而言之，这些结果有望更好地理解基于 CD 的超分子配合物的行为，例如吸附或聚集驱动力，以及引入能够加速一般 MD 模拟的新方法。
