Praseodymium chloride-mediated B-to-Z DNA transition in pyrimidine-purine repeat sequences: Simulation and biophysical study

The study investigates the impact of praseodymium chloride on the conformational transition between the B-form and Z-form of DNA. In the current communication, we employ a combination of biophysical techniques, including Circular dichroism, Isothermal titration calorimetry, Fourier transform infrared, Zeta potential and Molecular dynamics simulations to elucidate the mechanism of B-Z transition. Our results reveal a praseodymium-dependent modulation of the DNA helical structure, leading to the conversion from the canonical B-DNA to the left-handed Z-DNA in (CG)n repeat and condensation in (GC)n repeat. Altered helical parameters, base pair stacking and overall DNA geometry upon praseodymium binding has been characterized using spectroscopic analysis. The decrease in Gibbs free energy during ITC indicates a spontaneous reaction and provides the specific binding sites and coordination geometry of praseodymium ions within the DNA double helix. Molecular dynamics simulation further complements our experimental findings, offering a dynamic perspective on the temporal evolution of the B-Z transition process. We observe that praseodymium ions play a crucial role in stabilizing the Z-DNA conformation in (CG)n repeat, providing a foundation for understanding the thermodynamics and kinetics of this transition.