Microsolvation of Protonated Glycine: Infrared Spectra from Data-Driven Quantum Many-Body Simulations

Abstract

Abstract Understanding how hydration reshapes the structure and conformational flexibility of biomolecular ions is essential for connecting gas-phase spectroscopy to behavior in aqueous environments. Glycine, the simplest amino acid, exhibits rich microsolvation behavior, with competing intra- and intermolecular hydrogen-bonding motifs that evolve with hydration and temperature. Although cryogenic ion spectroscopy has provided detailed measurements of hydrated protonated glycine (GlyH+) clusters, interpreting these spectra and relating them to molecular hydration motifs remains challenging. Here, we develop a data-driven many-body potential energy function for GlyH+–H2O interactions and combine it with replica-exchange molecular dynamics to identify isomeric equilibria, and with temperature-elevated path-integral coarse-graining simulations to model GlyH+(H2O)n clusters, accounting for nuclear quantum effects. This framework captures many-body interactions with high-level ab initio accuracy and enables direct computation of infrared spectra for comparison with experiment. By applying an inverse spectral reconstruction of isomeric ensembles, we quantitatively decompose the experimental spectra into contributions from competing hydration motifs and extract their relative populations. Our results characterize the sequential formation of the first and second solvation shells, quantify the competition between intramolecular and water-mediated hydrogen bonds, and reveal temperature dependence and nuclear quantum effects. Overall, this study provides a transferable approach to understanding the hydration of biomolecular systems across scales, from gas-phase clusters to bulk aqueous solutions.