T-Life Research Center, Department of Physics, Fudan University, Shanghai 200433, China.
ACS Nano. 2010 Dec 28;4(12):7508-14. doi: 10.1021/nn101762b. Epub 2010 Nov 16.
Nanoscale particles have become promising materials in many fields, such as cancer therapeutics, diagnosis, imaging, drug delivery, catalysis, as well as biosensors. In order to stimulate and facilitate these applications, there is an urgent need for the understanding of the nanoparticle toxicity and other risks involved with these nanoparticles to human health. In this study, we use large-scale molecular dynamics simulations to study the interaction between several proteins (WW domains) and carbon nanotubes (one form of hydrophobic nanoparticles). We have found that the carbon nanotube can plug into the hydrophobic core of proteins to form stable complexes. This plugging of nanotubes disrupts and blocks the active sites of WW domains from binding to the corresponding ligands, thus leading to the loss of the original function of the proteins. The key to this observation is the hydrophobic interaction between the nanoparticle and the hydrophobic residues, particularly tryptophans, in the core of the domain. We believe that these findings might provide a novel route to the nanoparticle toxicity on the molecular level for the hydrophobic nanoparticles.
纳米颗粒在癌症治疗、诊断、成像、药物输送、催化以及生物传感器等多个领域已成为有前途的材料。为了激发和促进这些应用，人们迫切需要了解这些纳米颗粒对人类健康的毒性和其他风险。在这项研究中，我们使用大规模分子动力学模拟来研究几种蛋白质（WW 结构域）和碳纳米管（一种疏水性纳米颗粒）之间的相互作用。我们发现，碳纳米管可以插入蛋白质的疏水区核心，形成稳定的复合物。这种纳米管的插入会破坏和阻塞 WW 结构域与相应配体结合的活性位点，从而导致蛋白质失去原有的功能。这一观察结果的关键在于纳米颗粒与结构域核心中疏水性残基（特别是色氨酸）之间的疏水相互作用。我们相信，这些发现可能为疏水性纳米颗粒的纳米颗粒毒性提供了一种分子水平上的新途径。
