Zhai Yuanming, Deng Pengchi, Wang Xiaoyan, Zhang Chunchun, Gan Ruixue, Gan Na, Sun Qiaomei, Li Hui
Analytical & Testing Center, Sichuan University Chengdu 610064 China
School of Chemical Engineering, Sichuan University Chengdu 610065 China.
RSC Adv. 2018 Sep 10;8(55):31555-31563. doi: 10.1039/c8ra05330h. eCollection 2018 Sep 5.
The interaction mechanism between olaparib (OLA) and human serum albumin (HSA) has been investigated using experimental and computational techniques. An NMR relaxation approach based on the analysis of proton selective and non-selective spin-lattice relaxation rates at different temperatures can provide quantitative information about the affinity index and the thermodynamic equilibrium constant of the OLA-HSA system. The affinity index and the thermodynamic equilibrium constant decreased as temperature increased, indicating that the interactions between OLA and HSA could be weakened as temperature increased. Molecular docking and dynamics simulations revealed that OLA stably bound to subdomain II (site 1), and OLA could induce the conformational and micro-environmental changes in HSA. CD results suggested that α-helix content decreased after OLA was added, demonstrating that OLA affected the secondary structure of HSA.
已使用实验和计算技术研究了奥拉帕利（OLA）与人血清白蛋白（HSA）之间的相互作用机制。基于对不同温度下质子选择性和非选择性自旋晶格弛豫率分析的核磁共振弛豫方法，可以提供有关OLA-HSA系统的亲和指数和热力学平衡常数的定量信息。随着温度升高，亲和指数和热力学平衡常数降低，表明随着温度升高，OLA与HSA之间的相互作用可能会减弱。分子对接和动力学模拟表明，OLA稳定地结合到亚结构域II（位点1），并且OLA可以诱导HSA的构象和微环境变化。圆二色性结果表明，添加OLA后α-螺旋含量降低，表明OLA影响了HSA的二级结构。
