Native electrospray ionization mass spectrometry combined with molecular docking for the characterization of ginsenoside–myoglobin interactions

Abstract

Rationale: The interactions between proteins and ligands are involved in many biological processes and early stages of drug development. Native electrospray ionization mass spectrometry (native ESI-MS) has played an important role in the characterization of protein-ligand interactions. Herein, native ESI-MS combined with molecular docking was used for the characterization of ginsenoside-myoglobin (Mb) interactions. Methods: The binding of ginsenosides (Rb 3 , Rc, Rd, Re) to Mb was determined by native ESI-MS. Titration experiments were performed for the calculation of the dissociation constants (K d ) of the complexes. Molecular docking was used to simulate the binding of ginsenosides with Mb by AutoDock.Results: The ginsenoside-Mb complex with stoichiometric ratio 1:1 was observed by native ESI-MS. The K d values determined by the direct calculation method were matched with those obtained by the curve fitting method. However, the relative standard deviations (RSDs) obtained by direct calculation were larger than those obtained by curve fitting. From the molecular docking, it was inferred that hydrophobic interactions, hydrogen bonding and Van der Waals forces participate in the binding of ginsenosides to proteins. Conclusions:The ginsenoside-Mb interactions can be characterized by ESI-MS combined with molecular docking. This approach can be helpful to investigate the interactions between natural drugs and proteins in various diseases.