Dual-potential approach for coarse-grained implicit solvent models with accurate, internally consistent energetics and predictive transferability

Abstract

The dual-potential approach promises coarse-grained (CG) models that accurately reproduce both structural and energetic properties, while simultaneously providing predictive estimates for the temperature-dependence of the effective CG potentials. In this work, we examine the dual-potential approach for implicit solvent CG models that reflect large entropic effects from the eliminated solvent. Specifically, we construct implicit solvent models at various resolutions, R, by retaining a fraction 0.10 ≤ R ≤ 0.95 of the molecules from a simple fluid of Lennard-Jones spheres. We consider the dual-potential approach in both the constant volume and constant pressure ensembles across a relatively wide range of temperatures. We approximate the many-body potential of mean force for the remaining solutes with pair and volume potentials, which we determine via multiscale coarse-graining and self-consistent pressure-matching, respectively. Interestingly, with increasing temperature, the pair potentials appear increasingly attractive, while the volume potentials become increasingly repulsive. The dual-potential approach not only reproduces the atomic energetics but also quite accurately predicts this temperature-dependence. We also derive an exact relationship between the thermodynamic specific heat of an atomic model and the energetic fluctuations that are observable at the CG resolution. With this generalized fluctuation relationship, the approximate CG models quite accurately reproduce the thermodynamic specific heat of the underlying atomic model.