Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
PLoS One. 2011;6(6):e20925. doi: 10.1371/journal.pone.0020925. Epub 2011 Jun 7.
The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance.
蛋白质在无机表面的吸附具有重要的生物学意义。此外，生物医学和纳米技术应用越来越多地使用无机材料和多肽之间的界面。然而，多肽在表面上的吸附机制尚未得到很好的理解，实验分析也很困难。因此，我们使用具有极化金模型的显式水的计算分子动力学（MD）模拟来研究多肽与金（111）表面的相互作用。本文的重点是研究多肽与β-折叠结构的相互作用。首先，我们集中研究β-折叠形成模型肽。其次，我们研究了具有高β-折叠含量的生物重要细胞外基质蛋白纤维连接蛋白（FN）的两个结构域与金表面的相互作用。我们发现，对于模型肽和蛋白质，吸附都是通过逐步机制发生的。带正电荷的氨基酸精氨酸促进蛋白质与金表面之间初始接触的形成。我们的结果表明，有效的金结合表面区域整体上不带电荷，但包含用于接触起始的精氨酸。在模拟过程中，多肽不会在金表面上展开。然而，对于两个 FN 结构域，相对结构域-结构域取向发生变化。观察到非常快速和强烈的吸附表明，在生物基质中，不会存在裸露的金表面。因此，金表面的生物活性（如裸露的金纳米颗粒）将极大地取决于金与生物材料最初接触时颗粒的给药历史和存在的蛋白质。此外，金颗粒可能作为蛋白质聚集的种子。结构重组和蛋白质聚集具有潜在的免疫学意义。
