Molecular Insights into the Binding of Theophylline with DNA: An "In Silico" Approach.

This article ventures into the interactions between DNA and theophylline (Th), a biologically active xanthine derivative with pharmacological properties, using in-silico methods. Density functional theory calculations were used to assess the interactions between theophylline and natural nucleobases: adenine (A), guanine (G), cytosine (C), and thymine (T). Different interacting orientations, namely the planar hydrogen-bonded conformations and the vertically stacked geometries between theophylline and nucleobases have been investigated by evaluating the binding energies of the dimeric structures. The strength of hydrogen bonding between theophylline and nucleobases is found to be stronger compared to π-π stacking interactions, and hence, it is unlikely that theophylline would invade the DNA duplex and insert between nucleobases. Classical molecular dynamics simulations have been performed to gauge the interactions between theophylline and a DNA double helix. Theophylline is indeed observed to interact with DNA via hydrogen bonding rather than π-π stacking, keeping the DNA intact and eliminating any potential damage. Therefore, the adverse drug reactions of theophylline do not originate from the perturbation of DNA, and are of different origins. This research lays a solid groundwork and builds a deep understanding for future investigations aimed at studying interactions between theophylline and biomolecules.