Interaction of the protoberberine alkaloid coralyne with t-RNA^phe was investigated using various biophysical techniques. Results of absorption and fluorescence studies revealed that the alkaloid binds to t-RNA exhibiting positive cooperativity. Isothermal titration calorimetry results suggested that the binding of the alkaloid was predominantly enthalpy driven with a smaller favourable entropy term. A surprisingly large favourable component for non-electrostatic contribution to the binding of coralyne to t-RNA was revealed from salt dependence data and the dissection of the free energy. The alkaloid enhanced the thermal stability of t-RNA and the binding affinity values obtained from optical thermal melting data was in agreement with that from calorimetry. The heat capacity change of −125 cal mol⁻¹ K⁻¹ and the observed significant enthalpy–entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent interactions. Circular dichroism studies provided evidence for significant perturbation of the t-RNA structure with concomitant induction of optical activity in the bound achiral alkaloid molecules. Binding isotherms generated from circular dichroic data confirmed the cooperative binding mode of the alkaloid as deduced from spectroscopic data. Docking studies provided further insights into the partially intercalated state of coralyne inside the t-RNA structure. This study presents a complete binding and thermodynamic profile of coralyne interaction to t-RNA.

Binding of Nile Blue (NB) with calf thymus DNA has been studied using molecular modeling, spectroscopic, and thermodynamic techniques. Our study revealed that NB binds to the DNA helix by two types of modes (groove binding and intercalation) simultaneously. The thermodynamic study showed that the overall binding free energy is a combination of several negative and positive free energy changes. The binding was favored by negative enthalpy and positive entropy changes (due to the release of water from the DNA helix). The docking study validated all experimental evidence and showed that NB binds to a DNA minor groove at low concentrations and switches to intercalation mode at higher concentrations.