Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University, 1400 J.R. Lynch Street, P.O. Box 17910, Jackson, MS 39217, USA.
Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32/46, PL-02668 Warsaw, Poland.
Nanoscale. 2017 Jul 27;9(29):10263-10276. doi: 10.1039/c7nr00770a.
Fullerene-based nanoparticles have been the subject of vital interest due to their unique properties and potential application in many areas, including medicine. Here we explore their characteristics that could make them prospective leads for known disease-related proteins. High-throughput virtual screening supported by comprehensive multi-software protein-ligand docking simulation and cheminformatics approaches has been applied in investigation of interactions of 1117 proteins with a 169 fullerene nanoparticles decorated with different small molecules. Moreover, obtained docking results were confirmed by the series of unrestricted all-atom molecular dynamics (MD) simulations. Hydrophobicity of fullerene core along with hydrophilic interaction of side chains plays a key role in binding with the studied proteins. We identified a series of nanoparticles that can lead to development of robust drugs for target proteins and another series that can behave as a highly toxic agent. The structure-activity relationship analysis revealed two significant molecular properties responsible for the binding score values. The application of carefully selected computational techniques and described outcome of the study facilitate development of functional fullerene nanoparticles for drug-like and drug delivery applications.
由于富勒烯纳米粒子具有独特的性质和在许多领域（包括医学）的潜在应用，因此它们一直是人们关注的焦点。在这里，我们探讨了它们的特性，这些特性可能使它们成为已知与疾病相关的蛋白质的有前途的先导物。我们应用高通量虚拟筛选技术，结合全面的多软件蛋白质-配体对接模拟和化学信息学方法，研究了 1117 种蛋白质与 169 个富勒烯纳米粒子的相互作用，这些纳米粒子用不同的小分子进行了修饰。此外，还通过一系列无限制的全原子分子动力学（MD）模拟对获得的对接结果进行了验证。富勒烯核心的疏水性以及侧链的亲水相互作用在与研究蛋白的结合中起着关键作用。我们确定了一系列纳米粒子，它们可以为靶蛋白开发出有效的药物，而另一些纳米粒子则可以表现出很强的毒性。结构-活性关系分析揭示了两个负责结合评分值的重要分子特性。精心选择的计算技术的应用和研究结果的描述促进了具有类似药物特性和药物输送应用的功能性富勒烯纳米粒子的开发。
