Multi-spectroscopic, thermodynamic and molecular simulation studies on binding of pyrroloquinoline quinone with DNA: coexistence of intercalation and groove binding modes.

The interaction between enzyme-like pyrroloquinoline quinone () and calf-thymus DNA (CT-DNA) has been investigated by means of multi-spectroscopic (UV-Vis, fluorescence and circular dichroism), isothermal titration calorimetric (ITC), viscometry and molecular docking and metadynamics simulation techniques. Absorption spectral data suggested the formation of a /CT-DNA complex, which quenched the fluorescence of the dynamic quenching process. The results of CD spectral studies coupled with viscosity measurements, competitive binding assays with Hoechst 33258 and ethidium bromide (EB), KI quenching experiments, gel electrophoresis and DNA melting studies indicated groove binding mode of interaction of with CT-DNA. ITC experiment revealed that the complex formation is a spontaneous process (Δ < 0) with a binding constant of 1.05 × 10 M. The observed Δ < 0 and Δ < 0 pointed out that the complex is stabilized by van der Waals forces along with H-bonding interactions. The outcomes of molecular docking and simulation studies confirmed the binding of with DNA. The free energy surface (FES) analysis pointed out the existence of an equilibrium between partial intercalation and groove binding modes, which is in good agreement with the competitive binding assays.Communicated by Ramaswamy H. Sarma.