Short-Ranged United-Atom Model for Efficient Simulations of Glycerol and Its Aqueous Mixtures.

Abstract

Glycerol, a versatile cryoprotectant, exhibits a complex conformational landscape governed by intra- and intermolecular hydrogen bonds. Capturing its structural and thermodynamic properties in liquid and glass states remains challenging due to discrepancies between NMR, neutron scattering experiments, and all-atom (AA) simulations. While AA simulations are widely used, they overestimate the α-conformation and incur significant computational costs. Coarse-grained (CG) models provide an efficient alternative but have yet to accurately describe glycerol's conformational distribution and thermodynamic behavior. Here, we introduce SR-UA glycerol, a short-ranged united-atom model parametrized to reproduce experimental density, enthalpy of vaporization, conformational distributions from NMR, and radial distribution functions from neutron scattering data. Inspired by the monatomic water (mW) model, SR-UA glycerol employs short-range anisotropic interactions to mimic hydrogen bonding, achieving about 100-fold computational speedup over AA models. The model captures the conformational shift from γγ to αα as glycerol transitions from gas to the liquid phase, emphasizing the role of intermolecular hydrogen bonds in stabilizing open conformations. When combined with mW water, SR-UA glycerol successfully reproduces key features of glycerol-water mixtures, including the decrease in the temperature of maximum density and the dynamical crossover, in agreement with AA simulations across a range of temperatures and concentrations. This work establishes a robust and efficient model to investigate glycerol's behavior in aqueous mixtures, opening the possibility of addressing with molecular simulations the competition between vitrification and crystallization at cryopreservation-relevant conditions.