Study on the interaction of the bromodomain inhibitor JQ1 with human serum albumin by spectroscopic and molecular docking studies

Abstract

The present study examined the interaction of the bromodomain inhibitor/anti-cancer drug JQ1 with human serum albumin (HSA) by spectroscopic and molecular docking methods. Spectroscopic analysis of the fluorescence emission quenching at different temperatures and UV-vis spectroscopy revealed that the quenching mechanism of human serum albumin by JQ1 was static in nature. The quenching data was analyzed using Stern-Volmer equation. JQ1 was bound to HSA at only one site with a binding constant of 3.5 × 104 mol L−1 at 293 K. The binding site of JQ1 in HSA was identified as subdomain IIA in site I, predominantly interacting with Trp-214 residue present at the site I revealed by the site binding experiment. van't Hoff equation was applied to calculate thermodynamic parameters like enthalpy change (∆H°) -29.9 kJ/mol and entropy change (∆S°) +0.09 J/mol K at a temperature of 293 K. The negative value of ∆H° and positive ∆S° suggest the involvement of hydrogen bond and hydrophobic interactions as the predominant binding forces. Circular dichroism spectroscopy revealed that JQ1 induced a slight change in the secondary structure of HSA by reducing the percentage of α-helical content from 56.34% to 56.12%. Molecular docking studies showed that JQ1 majorly interacts with the amino acid residues present in the active site of site I through different types of interactions, including polar, hydrogen bond, electrostatic and hydrophobic interactions.