Exploring the binding mechanism of Pomalidomide drug with CT-DNA: Insights from multi-spectroscopic, molecular docking and simulation studies

Abstract

Exploration of the interaction of a thalidomide analogue immunomodulatory and anti-angiogenic drug pomalidomide (POD) with calf thymus DNA (CT-DNA) was carried out using multi-spectroscopic (UV–Vis, fluorescence, and circular dichroism), molecular docking and metadynamics simulation studies in Tris–HCl buffer (pH 7.4). The results revealed that POD binds to the nucleic acid via groove binding mode. The proposed binding mode is strongly supported by competitive dye displacement assay using ethidium bromide (EB) and rhodamine B (RB) dyes, KI quenching studies and viscosity measurements. The thermodynamic parameters such as ∆Ho (60 kJ mol−1), ∆So (297 JK−1 mol−1) and ∆Go (-22 kJ mol−1) indicated that the POD/CT-DNA interaction is spontaneous and is stabilized predominantly by hydrophobic forces. The proposed groove binding mode of interaction of POD with CT-DNA was further confirmed by a computer-aided molecular docking studies and analysis of free energy surface contour derived from the molecular simulation study.