Molecular mechanism and thermodynamic study of Rosuvastatin interaction with human serum albumin using a surface plasmon resonance method combined with a multi-spectroscopic, and molecular modeling approach

Rosuvastatin (ROS) is an anti-cholesterol drug belonging to statin drugs. A multi-spectroscopic approach combined with a molecular modeling technique was used to assess ROS association with human serum albumin (HSA). Besides, an HSA immobilized surface plasmon resonance (SPR) chip was used to obtain kinetic parameters (ka, kd, and K-D). Fluorescence quenching titrations revealed that ROS interacts with HSA via a dynamic, exothermic, enthalpy-driven mechanism. Hydrogen bonds and van der Waals interactions as the most prevalent bonding forces contribute to ROS-HSA complex formation. ROS binding to HSA alters HSA conformation. The SPR results indicated that ROS and HSA have a strong interaction possessing an equilibrium constant (K-D) of 1.55 x 10(-8) M at 298 K. A competitive analysis of site markers showed that ROS has a higher tendency to bind to the warfarin binding site (site IIA), which may explain why warfarin has a higher anticoagulant effect in ROS users. FRET analysis indicated that non-radiation energy transfer occurred between ROS and HSA. According to molecular docking studies, ROS prefers binding sites IB and IIA while the ROS-HSA complex stabilizes due to the hydrogen bond and pi-pi interaction. The presence of hydrogen-bond donors and acceptors, as well as aromatic ROS moieties, facilitates such interactions.

Automated summary

The research found that the binding mechanism between Rosuvastatin and human serum albumin is dynamic, exothermic, and enthalpy-driven, primarily through hydrogen bonds and van der Waals interactions. The formation of this complex alters the protein conformation and exhibits strong interaction. The results from surface plasmon resonance experiments showed that Rosuvastatin and human serum albumin have a stable binding.