The Theory of Ultra-Coarse-Graining. 3. Coarse-Grained Sites with Rapid Local Equilibrium of Internal States.

Abstract

When viewed through a coarse-grained lens, important molecular and biophysical systems can appear to undergo discrete, switch-like state changes in addition to more continuous configurational motions. One of our recent papers described a theory for bottom-up coarse-graining of the equilibrium statistics of models with such behavior, called ultra-coarse-grained (UCG) models, and a follow up paper described an implementation when the states of the coarse-grained sites or "beads" change rarely. However, not all systems with this discrete behavior fall under that special limit. This article develops the general UCG theory for the opposite limit, that is, where the internal states of the CG particles or beads adjust rapidly so as to always remain effectively at quasi-equilibrium no matter what the positions of the coarse-grained particles. This rapid local equilibrium allows ultra-coarse-graining to mix standard coarse-grained force fields by using local order parameters to control the degree of mixing, which adds an environmental dependence and many-body effects to the coarse-grained model while requiring minimal new coding. This article first presents the definition of such UCG force fields as well as their fitting procedures from atomistic-scale data, and then it presents three examples of UCG simulations with an approach that we call UCG with rapid local equilibrium (UCG-RLE). We then present an application of UCG-RLE using the full bottom-up methodology to coarse-grain and simulate cooperative hydrophobic association of neopentane in methanol solvent. UCG-RLE force matching does a superior job of matching solute-solute correlation functions and solute cluster size distributions compared to the more standard force-matched models not having coarse-grained sites with discrete internal states.