Department of Chemistry, Shiraz University, Shiraz, Iran.
J Pharm Biomed Anal. 2012 Aug-Sep;67-68:201-8. doi: 10.1016/j.jpba.2012.04.012. Epub 2012 Apr 17.
The interaction between harmalol and human serum albumin (HSA) has been studied by fluorescence spectroscopy and molecular modeling methods. The intrinsic fluorescence of HSA was quenched by harmalol, which was rationalized in terms of the static quenching mechanism. The binding parameters, quenching constants and conformation changes were determined by fluorescence quenching method. The thermodynamic parameters, calculated from the temperature dependence of binding constants (i.e., ΔH°=-62.7 kJ mol⁻¹ and ΔS°=-119.3J mol⁻¹ K⁻¹), indicated the major role of van der Waals force and hydrogen bonding in binding process. Site marker competitive experiments revealed that harmalol binds to both the IIA and IIIA sub-domains of HSA with a slight preference toward sub-domain IIA. Finally, the binding of harmalol to HSA was modeled by molecular docking and molecular dynamic simulation methods. Excellent agreement was found between the experimental and theoretical results with respect to the mechanism of binding and binding constants. Molecular dynamic simulation revealed that HSA does not have a significant conformational change when it binds with harmalol.
采用荧光光谱法和分子模拟方法研究了哈马林与人血清白蛋白（HSA）之间的相互作用。哈马林使 HSA 的内源性荧光猝灭，可以用静态猝灭机制来解释。通过荧光猝灭法确定了结合参数、猝灭常数和构象变化。根据结合常数的温度依赖性计算出热力学参数（即，ΔH°=-62.7kJmol⁻¹和ΔS°=-119.3Jmol⁻¹K⁻¹），表明范德华力和氢键在结合过程中起主要作用。位点标记竞争实验表明，哈马林与 HSA 的 IIA 和 IIIA 亚域结合，对亚域 IIA 略有偏好。最后，采用分子对接和分子动力学模拟方法对哈马林与 HSA 的结合进行了建模。结合机制和结合常数的实验和理论结果非常吻合。分子动力学模拟表明，HSA 与哈马林结合时没有明显的构象变化。
