Exothermic binding and structural alteration of the carrier protein lysozyme induced by Yohimbine: A spectroscopic, calorimetric and cheminformatic insight.

The crucial function of bioactive ligands in the interaction with diverse proteins has garnered significant attention in the fields of pharmacokinetics and pharmacodynamics, hence generating considerable interest in the discipline of medicinal chemistry. To better comprehend its molecular mechanism, we implored a detailed biophysical analyses (using multi-spectroscopic, calorimetric, and computational tools) of the carrier protein Lysozyme, Lyz (also known as "Muramidase") with Yohimbine (Yoh). The binding constant (K) of the Lyz-Yoh complex was estimated to be 105 M−1, exhibiting a progressive decline as temperature increased. The thermodynamic-profiling indicated the binding to be associated with an exothermic interaction driven by entropy. The confirmation of spontaneous binding is evidenced by the observed decrease in free energy. The variation in ionic strength indicated that non-polyelectrolytic forces were involved in the association. In addition, it was investigated how different metal ions affected the Lyz-Yoh binding. Calorimetric studies revealed the binding to be exothermic in nature, which also aligns with spectroscopic data. Results from circular dichroism (CD) experiments, demonstrated the structural alterations brought about in Lyz by Yoh. The likely binding sites and protein residuals to the ligand (Yoh) were illustrated using theoretical techniques, viz., molecular docking and molecular dynamic (MD) simulation. In clinical and pharmaceutical assessments, these metrics are especially relevant for rational drug development. [Display omitted] • Spontaneous and thermodynamically favorable association. • Competition between the metal ions and Yoh binding to Lyz at the same binding site. • A crucial role was played by the hydrophobic forces and hydrogen bonding. • Lyz microenvironmental changes after ligation with Yoh. [ABSTRACT FROM AUTHOR]