Exploring nucleotides complexes in solutions from spectroscopy and ab initio simulations

Emma Rossi, Laurie Stevens, Achintya Kundu, Thomas Elsaesser, Alberta Ferrarini, Marialore Sulpizi

Despite their fundamental relevance in biological processes and their applications in synthetic chemistry, elucidating the structure and dynamics of nucleotides complexes remains a non trivial task because of the presence of charges, highly polarizable species, solvent and conformational degrees of freedom.

Here I will address the characterization of adenosine triphosphate (ATP) -Zn complexes in a joint computational and experimental effort. We combine experimental measurements of the IR absorption spectra of ATP in water both in the absence and presence of Zn²⁺ with computed IR spectra from AIMD simulations of methyl triphosphate (MTP), a simplified model for ATP.

Performing accurate band assignments and structural characterizations, we show that water-triphosphate and metal-triphosphate interactions influence both frequency and coupling of asymmetric stretching of phosphate groups. The comparison between experimental and simulated spectra permits to identify the coordination modes of the ATP-Zn²⁺ complexes predominantly present in solution and to achieve a molecular understanding of the blueshift of the spectrum induced by the formation of the complex.

In the second part I will discuss how to overcome some limitation of the ab initio computational approach with the use of machine learning (ML) potentials, which permits to extend the range the applicability of such expensive methods to more realistic timescale. In particular, the conformational space of adenosine monophosphate (AMP) in solution is presented as a first test case, paving the way to more complex investigations.