A Statmech model of water that treats the solvation interface

Molecular simulations of biomolecules rely on either explicit water, which is computationally expensive, or implicit water, which can miss much of the interfacial physics. Here we develop a statistical mechanical model of liquid water and its interface with solutes. It has the advantages of being efficient -- because it is a computation, not a simulation -- and of capturing water's tetrahedral hydrogen bonding and spherical Lennard Jones interactions. It entails two steps. First, in Cage Water, we develop a reference state of pure water over the full liquid range vs (T, p) [Urbic, Dill, JACS, 2018]. Second, in Crust Water [Yadav et al, JPCB, 2022], we introduce a spherical solute molecule and populate the solute's surface (i.e. its crust) with these semi-explicit water molecules that we can compute efficiently. Now we further develop this model, more physically and accurately, by introducing ions and predicting ion solvation faithfully. We hope that further developments bring this approach into the computational modeling of biomolecules.