Fang Senbiao, Li Huanhuan, Liu Tao, Xuan Hongxia, Li Xin, Zhao Chunyan
School of Pharmacy, LanzhouUniversity, Lanzhou, 730000, China.
J Mol Model. 2014 Apr;20(4):2098. doi: 10.1007/s00894-014-2098-7. Epub 2014 Mar 16.
Polychlorinated biphenyls (PCBs) are potentially hazardous to the environment because of their chemical stability and biological toxicity. In this study, we identified the binding mode of a representative PCB180 to human serum albumin (HSA) using fluorescence and molecular dynamics (MD) simulation methods. PCB180 bound exactly at subdomain IIIA of HSA based on the fluorescence study along with site marker displacement experiments. PCB180 also induced conformational changes that were governed mainly by hydrophobic forces. MD studies and free energy calculations also made important contributions to the understanding of the effects of an HSA-PCB180 system on conformational changes. The simulations on binding behavior proved that PCB180 was located only in subdomain IIIA. Hydrophobic interactions dominated the mode of binding behavior. The results obtained using the two methods correlated well with each other. Our findings provide a framework for elucidating the mechanisms of PCB180-HSA binding, and may also help in further research on the transportation, distribution, and toxicity effects of PCBs when introduced into human blood serum.
多氯联苯（PCBs）因其化学稳定性和生物毒性而对环境具有潜在危害。在本研究中，我们使用荧光和分子动力学（MD）模拟方法确定了代表性的多氯联苯180（PCB180）与人血清白蛋白（HSA）的结合模式。基于荧光研究以及位点标记置换实验，PCB180精确地结合在HSA的亚结构域IIIA处。PCB180还诱导了主要由疏水作用力控制的构象变化。MD研究和自由能计算也对理解HSA - PCB180系统对构象变化的影响做出了重要贡献。结合行为的模拟证明PCB180仅位于亚结构域IIIA中。疏水相互作用主导了结合行为模式。使用这两种方法获得的结果相互关联良好。我们的研究结果为阐明PCB180 - HSA结合机制提供了一个框架，也可能有助于进一步研究多氯联苯引入人血清后的运输、分布和毒性效应。
