Probing the combination of erlotinib hydrochloride, an anticancer drug, and human serum albumin: Spectroscopic, molecular docking, and molecular dynamic analyses

Human serum albumin (HSA) is a globular and monomeric protein in plasma that transports many drugs and compounds. Binding of some drugs to HSA can lead to changes in its stability and biological function. We investigated the binding interactions between erlotinib hydrochloride (Erlo) and HSA. Erlo is used to treat lung, pancreatic, and some other cancers. Experimental data showed that the fluorescence emission of the protein was quenched by Erlo using a static quenching mechanism. The calculation of the binding constant, K-b (1.57 x 10(5) M-1 at 300 K), confirmed the existence of a moderate binding interaction between Erlo and HSA. The interaction was enthalpy driven, spontaneous, and exothermic. The calculated thermodynamic parameters in agreement with simulation and molecular docking data showed that van der Waals and hydrogen bond forces played an important role in the interaction process. Molecular docking results indicated that Erlo has more affinity to bind to subdomain IIA (site I) of HSA. Molecular dynamics simulation analysis showed that the protein is stable in the presence of Erlo under simulation conditions.

Automated summary

Human serum albumin (HSA) is a transport protein that binds to many drugs. This study investigated the binding interaction between erlotinib hydrochloride (Erlo) and HSA. The results showed that Erlo quenched the fluorescence emission of HSA through a static quenching mechanism. The binding between Erlo and HSA was moderate and driven by enthalpy, with van der Waals and hydrogen bond forces playing important roles.