Unravelling Binding of Human Serum Albumin with Galantamine: Spectroscopic, Calorimetric, and Computational Approaches
Ghulam Md Ashraf, Debarati Das Gupta, Mohammad Zubair Alam, Saleh Baeesa, Badrah S. Alghamdi, Firoz Anwar, Thamer Alqurashi, Waleed Al Abdulmonem, Mohammed Alyousef, Fahad A. Alhumaydhi, Anas Shamsi
Abstract
Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer's disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements. This study is carried out to understand the binding mechanism of GAL with HSA using computational and experimental approaches. Molecular docking revealed that GAL preferentially occupies Sudlow's site I, i.e., binds to subdomain IIIA. The results unveiled that GAL binding does not induce any conformational change in HSA and hence does not compromise the functionality of HSA. Molecular dynamics simulation (250 ns) deciphered the stability of the HSA-GAL complex. We performed the fluorescence binding and isothermal titration calorimetry (ITC) to analyze the actual binding of GAL with HSA. The results suggested that GAL binds to HSA with a significant binding affinity. ITC measurements also delineated thermodynamic parameters associated with the binding of GAL to HSA. Altogether, the present study deciphers the binding mechanism of GAL with HSA.