Drug-biomolecular interaction: Spectroscopic and computational insights into esomeprazole binding with human serum...

Cellular process relies on specific binding of drug molecules with desired biological receptors. Biomolecular receptors and drugs exhibit their biological functions upon their interactions. Understanding the binding parameters and energetics of the binding provides a plethora of information that may be helpful in drug design and discovery. Further, drug interaction with carrier proteins affects the pharmacokinetics and dynamics of other exogenous and endogenous drugs. In this work, we report the binding behavior of esomeprazole with human serum albumin using several biophysical techniques. Qualitative and quantitative aspects of the binding along with the binding energetics has been focused in extracting the thermodynamics parameters and key interaction force. The binding constants (K_b)obtained from Scatchard analysis are-1.17 × 10⁵, 7.49 × 10⁴, and 3.23 × 10⁴ M^-1 at 298, 303, 308 K respectively. Esomeprazole binds preferentially at site 1 in subdomain IIA of human serum albumin and was confirmed, supported by site-specific marker displacement studies and docking simulations. Negative value of change in free energy (∆G⁰) -32 kJ/mol at 298 K showed thermodynamically favourable interaction and outweigh of entropic factor (T∆S⁰ = 230.76 ± 3 kJ for T = 298 K) over the enthalpic contribution (∆H⁰ = -261.99 kJ/mol) revealed an entropy-driven process. Binding of esomeprazole affected the helical structure of human serum albumin. Molecular docking studies (theoretical) shows the binding pocket of ESM at site1(IIA), which is in accordance with the experimental result. Further, the interface residues involved in the binding were analysed from the 2D diagram and ligplot of the docked complex.