Interaction Between Ginkgolic Acid and Human Serum Albumin by Spectroscopy and Molecular Modeling Methods

The interaction of ginkgolic acid (15:1, GA) with human serum albumin (HSA) was investigated by FT-IR, CD and fluorescence spectroscopic methods as well as molecular modeling. FT-IR and CD spectroscopic showed that complexation with the drug alters the protein's conformation by a major reduction of alpha-helix from 54 % (free HSA) to 46-31 % (drug-complex), inducing a partial protein destabilization. Fluorescence emission spectra demonstrated that the fluorescence quenching of HSA by GA was by a static quenching process with binding constants on the order of 10(5) L center dot mol(-1). The thermodynamic parameters (Delta H = -28.26 kJ center dot mol(-1), Delta S = 11.55 J center dot mol(-1)center dot K-1) indicate that hydrophobic forces play a leading role in the formation of the GA-HSA complex. The ratio of GA and HSA in the complex is 1:1 and the binding distance between them was calculated as 2.2 nm based on the Forster theory, which indicates that the energy transfer from the tryptophan residue in HSA to GA occurs with high probability. On the other hand, molecular docking studies reveal that GA binds to Site II of HSA (sub-domain IIIA), and it also shows that several amino acids participate in drug-protein complexation, which is stabilized by H-bonding.