ATP AND ITS COMPLEX WITH DIVALENT IONS IN WATER: NEW INSIGHT IN A STILL PUZZLING SYSTEM

Beyond its outstanding role as the energy currency of the cell, adenosine 5'-triphosphate (ATP) has unique features underlying its relevance to biological processes and the design of bioinspired synthetic systems. The principles governing the multifaceted role of ATP are encoded in its molecular structure, which combines moieties of different chemical nature, i.e. a charged triphosphate group, a polar sugar, and an aromatic purinic base, which establish diverse interactions with the surroundings. ATP exerts diversified effects in phenomena such as protein folding, phase separation and aggregation, which cannot be fully rationalized by categorizing it as a simple amphiphile. Experimental techniques may lack sufficient spatial and temporal resolution to provide insights into these aspects at the molecular level, whereas computational methods serve as valuable tools. This Thesis focuses on the characterization of ATP conformational, metal coordination and solvation properties in water - a fundamental step towards the understanding of ATP special behaviour in more complex environments. Molecular dynamics simulations across different time and length scales were employed, also in combination with spectroscopic techniques. Enhanced sampling simulations revealed the limitations of currently available empirical models for ATP and its complexes with divalent ions in water, for which different binding modes are predicted depending on the description of the conformations of the single nucleotide. An integrated approach of infrared spectroscopy and ab initio molecular dynamics allowed the identification of the most stable coordination modes of ATP-Zn2+ and highlighted conformational disorder, reflecting the coordination flexibility and solvation dynamics. The interplay between ATP and its water environment remains a hotly debated topic, particularly regarding unexplored functions of this molecule in biomolecular processes. A computational study, conducted as part of a collaborative project involving Terahertz spectroscopy experiments, allowed us to characterize water dynamics in hydration shells of ATP subunits, where long range water-water correlations induced by the solute were found to play a decisive role in defining the spectral line shape