Combined fluorescence spectroscopy and molecular modeling studies on the interaction between harmalol and human serum albumin

[Display omitted] ► The interaction between harmalol and human serum albumin has been investigated. ► The results obtained revealed that harmalol has moderate affinities for HSA and binds mainly to subdomain IIA. ► Hydrogen bonding formation and van der Waals forces play major role in the binding process. ► Excellent agreement was found between the experimental and theoretical results regarding the mechanism of binding and binding constants. 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°=−62.7kJmol−1 and ΔS°=−119.3Jmol−1K−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.