J Chem Theory Comput. 2022 Aug 24. doi: 10.1021/acs.jctc.2c00248. Online ahead of print.
Molecular assembly processes are generally driven by thermodynamic properties in solutions. Atomistic modeling can be very helpful in designing and understanding complex systems, except that bulk solvent is very inefficient to treat explicitly as discrete molecules. In this work, we develop and assess two multiscale solvation models for computing solvation thermodynamic properties. The new SLIC/CDC model combines continuum solvent electrostatics based on the solvent layer interface condition (SLIC) with new statistical thermodynamic models for hydrogen bonding and nonpolar modes: cavity formation, dispersion interactions, combinatorial mixing (CDC). Given the structures of 500 solutes, the SLIC/CDC model predicts Gibbs energies of solvation in water with an average accuracy better than 1 kcal/mol, when compared to experimental measurements, and better than 0.8 kcal/mol, when compared to explicit-solvent molecular dynamics simulations. The individual SLIC/CDC energy mode values agree quantitatively with those computed from explicit-solvent molecular dynamics. The previously published SLIC/SASA multiscale model combines the SLIC continuum electrostatic model with the solvent-accessible surface area (SASA) nonpolar energy mode. With our new, improved parametrization method, the SLIC/SASA model now predicts Gibbs energies of solvation with better than 1.4 kcal/mol average accuracy in aqueous systems, compared to experimental and explicit-solvent molecular dynamics, and better than 1.6 kcal/mol average accuracy in ionic liquids, compared to explicit-solvent molecular dynamics. Both models predict solvation entropies, and are the first implicit-solvation models capable of predicting solvation heat capacities.