Exploring the interaction between JQ1 and IgG: An integrative multispectroscopic and in-silico approach

JQ1, a potent bromodomain inhibitor of BET proteins, has gained significant interest for its anticancer potential. However, its clinical use is limited by its very short half-life in circulation. Investigating the interaction of JQ1 with serum proteins provides an alternative method to enhance its stability and prolong the circulation time. Our previous reports revealed the potential binding of JQ1 with human serum albumin (HSA). In this study, we explored the interactions of JQ1 with Immunoglobulin G (IgG), another major serum protein, using spectroscopic and in-silico methods. UV–visible and fluorescence techniques showed static quenching and stable JQ1–IgG complex formation. Stern-Volmer analysis yielded a binding constant of 8.36 × 10⁴ L mol⁻¹ at 298 K, and n ≈ 1 from the double-logarithmic plot indicating single-site binding. Thermodynamic parameters (ΔH⁰ = − 48.35 kJ mol⁻¹ and ΔS⁰ = −182.1 mol⁻¹ K⁻¹) suggest spontaneous binding dominated by hydrogen bonding and Van der Waals forces. Circular dichroism revealed a slight increase in IgG β-sheet content from 45.1% to 49.9%, indicating conformational stabilization. Molecular docking and molecular dynamics simulations further supported the experimental findings, showing that JQ1 occupies binding pockets in the Fab and Fc regions, stabilized primarily by hydrogen bonding and π–π stacking interactions. MM-GBSA binding energy calculations also highlighted Van der Waals-dominated interactions, particularly in the Fc region. Collectively, this study provides spectroscopic and computational evidence of the IgG-JQ1 interaction, suggesting that IgG can influence the pharmacokinetics of JQ1 under physiological conditions.