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

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.