Exploring the binding mechanism of Guaijaverin to human serum albumin: Fluorescence spectroscopy and computational approach

The Guaijaverin (Gua) is a polyphenolic substance which exhibits some pharmacological activities such as antibacterial and antioxidant activities. Here we have investigated the binding of Gua with human serum albumin (HSA) at physiological pH 7.0. In this study, the fluorescence spectroscopy, ab initio and molecular modeling calculations were applied. The Stern–Volmer quenching constant (KSV) and its modified form (Ka) were calculated at 298, 303 and 308 K, with the corresponding thermodynamic parameters ΔH, ΔG and ΔS as well. The fluorescence quenching method was used to determine the number of binding sites (n) and binding constants (Kb) values at 298, 303 and 308 K. The distance between donor (HSA) and acceptor (Gua) was estimated according to fluorescence resonance energy transfer. The geometry optimization of Gua was performed in its ground state by using ab initio DFT/B3LYP functional with a 6-31G(d,p) basis set used in calculations. Molecular modeling calculation indicated that the Gua is located within the hydrophobic pocket of the subdomain IIA of HSA. The theoretical results obtained by molecular modeling were corroborated by fluorescence spectroscopy data.

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► The quenching mechanism between Gua and HSA is a static process.
► Gua molecule binds to the site I of HSA interacting close to the Trp214 residue.
► Enthalpic and entropic balanced forces stabilize the complexation.
► Molecular modeling simulations agree with the fluorescence spectroscopy analysis.