Dispersion interactions in fluorinated biopolymers

生物聚合物的结构和功能取决于不同类型相互作用的平衡：静电，分散和疏水相互作用。后者对于理解非极性溶质在水环境中聚集的“疏水效应”具有重要意义。因此，分散相互作用在生物聚合物的结构和动力学中起着重要作用，导致和稳定蛋白质组装。氟化已被证明通过改变静电和分散相互作用之间的平衡来调节小分子的性质。对于肽、蛋白质和其他生物聚合物，可以预期类似的效果。为了探索水合生物聚合物的影响，我们将采用分子模拟在原子水平的细节，与我们的合作伙伴提供的拉曼实验。氟化和非氟化小分子在气相和溶液中的第一性原理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参考数据的经典力场参数的发展。使用这些参数，经典的分子动力学模拟在更大的规模上将揭示的影响，在生物聚合物中的分散相互作用和它们的依赖于聚合物的长度，构象，和结构的灵活性上的双折射。这些方面，这是重要的蛋白质，不能在非常小的分子通常用作氨基酸侧链的类似物进行研究。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。我们的模拟选择性氟化的生物聚合物将探测分散相互作用是否是疏水吸引力的主要贡献，从而可以解释氟化蛋白质结构和结构稳定性的变化。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。

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.