氯化胆碱作为纳米拥挤剂保护HP-36免受尿素诱导的变性：溶剂动力学和蛋白质-溶剂相互作用的见解
Choline chloride as a nano-crowder protects HP-36 from urea-induced denaturation: Insights from Solvent Dynamics and Protein-Solvent interaction
摘要：
足够高浓度的尿素使蛋白质的二级结构展开，导致变性。相比之下，氯化胆碱（ChCl）和尿素以1：2的摩尔比形成深共熔混合物，在室温下为液体，并保护蛋白质免于变性。为了得到这一现象的微观图像，我们对模型蛋白HP-36进行了广泛的全原子分子动力学模拟。基于我们计算的Kirkwood-Buff积分，我们分析了这些渗透剂在蛋白质周围的相对积累。从溶剂分子的平移和旋转动力学的分析，也从氢键自关联函数的其他见解。在尿素的存在下，水表现出缓慢的亚扩散动力学周围的蛋白质骨架作为一个结果，更强的相互作用的水分子与骨架原子。尿素也表现出亚扩散运动。胆碱的添加进一步减慢尿素的动力学，限制其包含在蛋白质骨架周围。此外，胆碱分子在第一溶剂化壳的蛋白质显示出最强的亚扩散行为。换句话说，ChCl通过将尿素从蛋白质骨架中排除，从而减缓蛋白质周围水层的动力学，表现为纳米拥挤剂。这防止了蛋白质变性，并使其结构刚性，这反过来又得到了系统中存在ChCl时HP-36的较小回转半径和均方根偏差值的支持。
英文摘要：
Urea at sufficiently high concentration unfolds the secondary structure of proteins leading to denaturation. In contrast, Choline Chloride (ChCl) and urea, in 1:2 molar ratio form a deep eutectic mixture, a liquid at room temperature and protect proteins from denaturation. In order to get a microscopic picture of this phenomenon, we perform extensive all-atom molecular dynamics simulations on a model protein HP-36. Based on our calculation of Kirkwood-Buff integrals, we analyze the relative accumulation of these osmolytes around the protein. Additional insights are drawn from the analyses of the translational and rotational dynamics of solvent molecules and also from the hydrogen bond auto-correlation functions. In the presence of urea, water shows slow subdiffusive dynamics around the protein backbone as a consequence of stronger interaction of water molecules with the backbone atoms. Urea also shows subdiffusive motion. Addition of choline further slows down the dynamics of urea restricting its inclusion around the protein backbone. Adding to this, choline molecules in the first solvation shell of the protein shows the strongest subdiffusive behavior. In other words, ChCl behaves as a nano-crowder by excluding urea from the protein backbone and thereby slowing down the dynamics of the water layer around the protein. This prevents the protein from denaturation and makes it structurally rigid which in turn is supported by the smaller radius of gyration and root mean square deviation values of HP-36 when ChCl is present in the system.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
