Department of Chemical Engineering, University of California, Santa Barbara, California 93106, United States.
Department of Chemical Engineering, University of Puerto Rico, Mayagüez, Puerto Rico 00681, United States.
Biomacromolecules. 2022 Apr 11;23(4):1745-1756. doi: 10.1021/acs.biomac.1c01687. Epub 2022 Mar 11.
We use molecular dynamics simulations to investigate the effect of polypeptoid sequence on the structure and dynamics of its hydration waters. Polypeptoids provide an excellent platform to study small-molecule hydration in disordered polymers, as they can be precisely synthesized with a variety of sidechain chemistries. We examine water behavior near a set of peptoid oligomers in which the number and placement of nonpolar versus polar sidechains are systematically varied. To do this, we leverage a new computational workflow enabling accurate sampling of polypeptoid conformations. We find that the hydration waters are less dense, are more tetrahedral, and have slower dynamics compared to bulk water. The magnitude of these shifts increases with the number of nonpolar groups. We also find that shifts in the water structure and dynamics are strongly correlated, suggesting that experimental insight into the dynamics of hydration water obtained by Overhauser dynamic nuclear polarization (ODNP) also contains information about water structural properties. We then demonstrate the ability of ODNP to probe site-specific dynamics of hydration water near these model peptoid systems.
我们使用分子动力学模拟来研究多肽序列对其水合水分子结构和动力学的影响。多肽类提供了一个极好的平台来研究无序聚合物中的小分子水合作用，因为它们可以通过各种侧链化学精确合成。我们研究了一组肽寡聚物附近水的行为，其中非极性与极性侧链的数量和位置被系统地改变。为此，我们利用一种新的计算工作流程，能够准确地采样多肽构象。我们发现，与本体水相比，水合水分子密度更低、具有更规则的四面体结构且动力学更慢。这些变化的幅度随着非极性基团数量的增加而增加。我们还发现，水结构和动力学的变化具有很强的相关性，这表明通过过氧乙酰硝酸酯动态核极化（ODNP）实验获得的水合水分子动力学的实验洞察力也包含了有关水结构特性的信息。然后，我们展示了 ODNP 探测这些模型肽系统附近水合水分子的特定位置动态的能力。
