Unveiling the Binding Dynamics of two organic compounds with Human Serum Albumin: Integrating Computational, Spectroscopic, and Preliminary Single-Crystal X-ray Diffraction (SCXRD) Insights

This study investigates the interactions between human serum albumin (HSA) and two detergents, propylene carbonate (PC) and decyl glucoside (DG), using a combination of experimental and computational approaches. Albumin, a highly abundant and multifunctional non-glycosylated protein, plays a crucial role in various physiological processes and exhibits significant changes in plasma levels in response to inflammation. To understand the binding affinity and stability of these detergents with HSA, we employed molecular docking, molecular dynamics (MD) simulations, UV–visible spectroscopy, and preliminary single-crystal X-ray diffraction (SCXRD) analysis. Molecular docking studies revealed that DG binds more effectively to HSA than PC, as indicated by lower free energy of binding (FEB) values. MD simulations provided insights into the stability of the HSA–detergent complexes, showing that while the ligand remained relatively stable, a slight repositioning occurred during the simulation. UV–visible absorption spectroscopy confirmed the interaction of both PC and DG with HSA, evidenced by changes in the absorption spectrum, particularly around 280 nm. Preliminary SCXRD analysis of HSA crystals indicated successful crystallization, though attempts to crystallize the HSA-PC complex were unsuccessful. Overall, this study highlights the binding affinities and interaction dynamics of PC and DG with HSA, emphasizing the impact of these interactions on albumin's functionality. The integration of experimental data and computational modeling offers a comprehensive understanding of these molecular interactions, potentially guiding future research and applications in biological and industrial contexts.