State Key Laboratory of Virology, College of Life Sciences, Center of Nanoscience and Nanotechnology, Wuhan University, Wuhan 430072, China.
J Phys Chem B. 2010 Oct 14;114(40):12938-47. doi: 10.1021/jp102053x.
Pharmaceutical interactions with human serum albumin (HSA) are of great interest, because HSA is a pharmacokinetic determinant and a good model for exploring the protein-ligand interactions. Due to their hydrophobic nature, naturally occurring flavones, which possess various pharmacological activities, bind to HSA in human plasma. Here, we have identified the binding modes of two representative flavones--baicalin (BLI) and its aglycon, baicalein (BLE)--to HSA using a combination of experimental and computational approaches. The association properties were measured by applying spectroscopic methods, and a higher affinity was found for BLE. As evidenced by displacement and chemical unfolding assays, both ligands bind at Sudlow site I. Furthermore, molecular docking was utilized to characterize the models of HSA-flavone complexes, and molecular dynamics (MD) simulations as well as free energy calculations were undertaken to examine the energy contributions and the roles of various amino acid residues of HSA in flavones binding; the mechanism whereby glycosylation affects the association was also discussed. The present work provides reasonable binding models for both flavones to HSA.
药物与人体血清白蛋白（HSA）的相互作用是非常重要的，因为 HSA 是一个药代动力学决定因素，也是探索蛋白质-配体相互作用的良好模型。由于其疏水性，具有各种药理活性的天然黄酮类化合物在人血浆中与 HSA 结合。在这里，我们使用实验和计算相结合的方法，确定了两种代表性的黄酮类化合物——黄芩苷（BLI）及其苷元黄芩素（BLE）与 HSA 的结合模式。通过应用光谱方法测量了结合特性，发现 BLE 的亲和力更高。如置换和化学展开测定所证明的，两种配体均结合在 Sudlow 位点 I 上。此外，还利用分子对接来描述 HSA-黄酮类复合物的模型，并进行分子动力学（MD）模拟和自由能计算，以检查 HSA 中各种氨基酸残基在黄酮类化合物结合中的能量贡献和作用;还讨论了糖基化如何影响结合的机制。本工作为两种黄酮类化合物与 HSA 的结合提供了合理的结合模型。
