Exploring the landscape of model representations.

The success of any physical model critically depends upon adopting an appropriate representation for the phenomenon of interest. Unfortunately, it remains generally challenging to identify the essential degrees of freedom or, equivalently, the proper order parameters for describing complex phenomena. Here we develop a statistical physics framework for exploring and quantitatively characterizing the space of order parameters for representing physical systems. Specifically, we examine the space of low-resolution representations that correspond to particle-based coarse-grained (CG) models for a simple microscopic model of protein fluctuations. We employ Monte Carlo (MC) methods to sample this space and determine the density of states for CG representations as a function of their ability to preserve the configurational information, I, and large-scale fluctuations, Q, of the microscopic model. These two metrics are uncorrelated in high-resolution representations but become anticorrelated at lower resolutions. Moreover, our MC simulations suggest an emergent length scale for coarse-graining proteins, as well as a qualitative distinction between good and bad representations of proteins. Finally, we relate our work to recent approaches for clustering graphs and detecting communities in networks.

Van der Waals Perspective on Coarse-Graining: Progress toward Solving Representability and Transferability Problems.

Low-resolution coarse-grained (CG) models provide the necessary efficiency for simulating phenomena that are inaccessible to more detailed models. However, in order to realize their considerable promise, CG models must accurately describe the relevant physical forces and provide useful predictions. By formally integrating out the unnecessary details from an all-atom (AA) model, "bottom-up" approaches can, at least in principle, quantitatively reproduce the structural and thermodynamic properties of the AA model that are observable at the CG resolution. In practice, though, bottom-up approaches only approximate this "exact coarse-graining" procedure. The resulting models typically reproduce the intermolecular structure of AA models at a single thermodynamic state point but often describe other state points less accurately and, moreover, tend to provide a poor description of thermodynamic properties. These two limitations have been coined the "transferability" and "representability" problems, respectively. Perhaps, the simplest and most commonly discussed manifestation of the representability problem regards the tendency of structure-based CG models to dramatically overestimate the pressure. Furthermore, when these models are adjusted to reproduce the pressure, they provide a poor description of the compressibility. More generally, it is sometimes suggested that CG models are fundamentally incapable of reproducing both structural and thermodynamic properties. After all, there is no such thing as a "free lunch"; any significant gain in computational efficiency should come at the cost of significant model limitations. At least in the case of structural and thermodynamic properties, though, we optimistically propose that this may be a false dichotomy. Accordingly, we have recently re-examined the "exact coarse-graining" procedure and investigated the intrinsic consequences of representing an AA model in reduced resolution. These studies clarify the origin and inter-relationship of representability and transferability problems. Both arise as consequences of transferring thermodynamic information from the high resolution configuration space and encoding this information into the many-body potential of mean force (PMF), that is, the potential that emerges from an exact coarse-graining procedure. At least in principle, both representability and transferability problems can be resolved by properly addressing this thermodynamic information. In particular, we have demonstrated that "pressure-matching" provides a practical and rigorous means for addressing the density dependence of the PMF. The resulting bottom-up models accurately reproduce the structure, equilibrium density, compressibility, and pressure equation of state for AA models of molecular liquids. Additionally, we have extended this approach to develop transferable potentials that provide similar accuracy for heptane-toluene mixtures. Moreover, these potentials provide predictive accuracy for modeling concentrations that were not considered in their parametrization. More generally, this work suggests a "van der Waals" perspective on coarse-graining, in which conventional structure-based methods accurately describe the configuration dependence of the PMF, while independent variational principles infer the thermodynamic information that is necessary to resolve representability and transferability problems.

The impact of resolution upon entropy and information in coarse-grained models.

By eliminating unnecessary degrees of freedom, coarse-grained (CG) models tremendously facilitate numerical calculations and theoretical analyses of complex phenomena. However, their success critically depends upon the representation of the system and the effective potential that governs the CG degrees of freedom. This work investigates the relationship between the CG representation and the many-body potential of mean force (PMF), W, which is the appropriate effective potential for a CG model that exactly preserves the structural and thermodynamic properties of a given high resolution model. In particular, we investigate the entropic component of the PMF and its dependence upon the CG resolution. This entropic component, SW, is a configuration-dependent relative entropy that determines the temperature dependence of W. As a direct consequence of eliminating high resolution details from the CG model, the coarsening process transfers configurational entropy and information from the configuration space into SW. In order to further investigate these general results, we consider the popular Gaussian Network Model (GNM) for protein conformational fluctuations. We analytically derive the exact PMF for the GNM as a function of the CG representation. In the case of the GNM, -TSW is a positive, configuration-independent term that depends upon the temperature, the complexity of the protein interaction network, and the details of the CG representation. This entropic term demonstrates similar behavior for seven model proteins and also suggests, in each case, that certain resolutions provide a more efficient description of protein fluctuations. These results may provide general insight into the role of resolution for determining the information content, thermodynamic properties, and transferability of CG models. Ultimately, they may lead to a rigorous and systematic framework for optimizing the representation of CG models.