Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA.
Nanoscale. 2014 Jul 21;6(14):8340-9. doi: 10.1039/c4nr01544d.
Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation - a common strategy for solubilizing and functionalizing fullerene - on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding.
富勒烯及其具有不同表面化学性质的衍生物在生物医学应用中具有巨大的潜力。因此，阐明这些碳基纳米粒子对蛋白质结构、动力学以及随后的功能的影响非常重要。在这里，我们专注于通过一种模型蛋白——泛素，来研究羟化——一种常用的富勒烯增溶和功能化策略——对蛋白-纳米粒子相互作用的影响。我们应用了一系列互补的计算建模方法，包括对接和带有显式和隐式溶剂的分子动力学模拟，以说明羟化富勒烯对泛素结构和动力学的影响。我们发现所有衍生物都与模型蛋白结合。具体来说，具有更多亲水性和更多羟基的纳米粒子通过氢键与蛋白质表面结合，从而稳定蛋白质，而不会引起蛋白质结构的大构象变化。相比之下，具有较少羟基的富勒烯衍生物将其疏水性表面埋藏在蛋白质内部，从而导致蛋白质变性。总的来说，我们的结果揭示了表面化学在纳米粒子-蛋白结合和结合诱导的蛋白错误折叠中的明显作用。
