Dispersion interactions in fluorinated biopolymers

氟化生物聚合物中的分散相互作用

• 批准号: 398048621
• 负责人: Dr. Ana Vila Verde, since 4/2019
• 金额: --
• 依托单位: Forschungsgruppe Theoretische Physik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/398048621?language=en
• 关键词: Dispersion; interactions; fluorinated; biopolymers

The structure and function of biopolymers are determined by the balance of different types of interactions: electrostatic, dispersion, and hydrophobic interactions. The latter are important in understanding the “hydrophobic effect” associated with aggregation of apolar solutes in aqueous environment. Dispersion interactions thus play a major role in the biopolymer structure and dynamics, leading to and stabilizing protein assemblies. Fluorination has been shown to modulate the properties of small molecules by altering the balance between electrostatic and dispersion interactions. Similar effects can be expected for peptides, proteins and other biopolymers. To explore the impact of fluorination on hydrated biopolymers, we will employ molecular simulations at atomic level detail, in comparison with Raman experiments provided by our collaboration partners. First principles simulations of fluorinated and non-fluorinated small molecules in gas phase and in solution will allow us to dissect the balance of electrostatic and dispersive interactions on an electronic structure level. These calculations will furthermore serve as reference data for the development of classical force field parameters. Using these parameters, classical molecular dynamics simulations on a larger scale will reveal the impact of fluorination on the dispersion interactions in biopolymers and their dependence on polymer length, conformation, and structural flexibility. These aspects, which are important for proteins, cannot be studied in the very small molecules typically used as analogues of amino acid side chains. However, direct dispersive interactions between hydrophobic groups in solution do depend on the distance of these groups and thus the shape and conformational dynamics of the polymer. Our simulations of selectively fluorinated biopolymers will probe whether dispersion interactions are the dominant contribution to hydrophobic attraction and may thus account for changes in protein structure and structural stability in fluorinated proteins. This understanding can ultimately be used to modify the balance of the different interactions and thereby control protein properties via specific fluor-substitution.

生物聚合物的结构和功能取决于不同类型的相互作用的平衡：静电作用、分散作用和疏水作用。后者对于理解非极溶质在水环境中聚集的“疏水效应”很重要。因此，分散相互作用在生物聚合物的结构和动力学中起着主要作用，导致和稳定蛋白质组装。氟化已被证明通过改变静电和色散相互作用之间的平衡来调节小分子的性质。多肽、蛋白质和其他生物聚合物也会产生类似的影响。为了探索氟化对水合生物聚合物的影响，我们将使用原子水平的详细分子模拟，并与我们的合作伙伴提供的拉曼实验进行比较。第一原理对气相和溶液中的氟化和非氟化小分子的模拟将使我们能够在电子结构水平上剖析静电和色散相互作用的平衡。这些计算将进一步作为发展经典力场参数的参考数据。使用这些参数，更大规模的经典分子动力学模拟将揭示氟化作用对生物聚合物中分散相互作用的影响，以及它们对聚合物长度、构象和结构柔性的依赖关系。这些对蛋白质很重要的方面，不能在通常用作氨基酸侧链类似物的非常小的分子中进行研究。然而，溶液中疏水基团之间的直接分散相互作用确实取决于这些基团的距离，从而取决于聚合物的形状和构象动力学。我们对选择性氟化生物聚合物的模拟将探索分散相互作用是否是疏水吸引力的主要贡献，并因此可能解释蛋白质结构的变化和氟化蛋白质的结构稳定性。这种理解最终可以用来改变不同相互作用的平衡，从而通过特定的氟取代来控制蛋白质的性质。