Coarse-grained models for local density gradients.

Coarse-grained (CG) models provide superior computational efficiency for simulating soft materials. Unfortunately, CG models with conventional pair-additive potentials demonstrate limited transferability between bulk and interfacial environments. Recently, a growing number of CG models have supplemented these pair potentials with one-body potentials of the local density (LD) around each site. These LD potentials can significantly improve the accuracy and transferability of CG models. Nevertheless, it remains challenging to accurately describe interfaces where the LD varies rapidly. In this work, we consider a new class of one-body potentials that depend upon the square of the LD gradient around each site. We investigate the impact of this square gradient (SG) potential upon both top-down dissipative particle dynamics (DPD) models and also bottom-up multiscale coarse-graining (MS-CG) models. We demonstrate that SG potentials can be used to tune the interfacial properties of DPD models without significantly altering their bulk properties. Moreover, we demonstrate that SG potentials can improve the bulk pressure-density equation of state as well as the interfacial profile of MS-CG models for acetic acid. Consequently, SG potentials may provide a useful connection between particle-based top-down models and mean-field Landau theories for phase behavior. Furthermore, SG potentials may prove useful for improving the accuracy and transferability of bottom-up CG models for interfaces and other inhomogeneous systems with significant density gradients.

Bottom-up coarse-grained models for external fields and interfaces.

Bottom-up coarse-grained (CG) models accurately describe the structure of homogeneous systems but sometimes provide limited transferability and a poor description of thermodynamic properties. Consequently, inhomogeneous systems present a severe challenge for bottom-up models. In this work, we examine bottom-up CG models for interfaces and inhomogeneous systems. We first analyze the effect of external fields upon the many-body potential of mean force. We also demonstrate that the multiscale CG (MS-CG) variational principle for modeling the external field corresponds to a generalization of the first Yvon-Born-Green equation. This provides an important connection with liquid state theory, as well as physical insight into the structure of interfaces and the resulting MS-CG models. We then develop and assess MS-CG models for a film of liquid methanol that is adsorbed on an attractive wall and in coexistence with its vapor phase. While pair-additive potentials provide unsatisfactory accuracy and transferability, the inclusion of local-density (LD) potentials dramatically improves the accuracy and transferability of the MS-CG model. The MS-CG model with LD potentials quite accurately describes the wall-liquid interface, the bulk liquid density, and the liquid-vapor interface while simultaneously providing a much improved description of the vapor phase. This model also provides an excellent description of the pair structure and pressure-density equation of state for the bulk liquid. Thus, LD potentials hold considerable promise for transferable bottom-up models that accurately describe the structure and thermodynamic properties of both bulk and interfacial systems.

Analysis of local density potentials.

Low resolution coarse-grained (CG) models are widely adopted for investigating phenomena that cannot be effectively simulated with all-atom (AA) models. Since the development of the many-body dissipative particle dynamics method, CG models have increasingly supplemented conventional pair potentials with one-body potentials of the local density (LD) around each site. These LD potentials appear to significantly extend the transferability of CG models, while also enabling more accurate descriptions of thermodynamic properties, interfacial phenomena, and many-body correlations. In this work, we systematically examine the properties of LD potentials. We first derive and numerically demonstrate a nontrivial transformation of pair and LD potentials that leaves the total forces and equilibrium distribution invariant. Consequently, the pair and LD potentials determined via bottom-up methods are not unique. We then investigate the sensitivity of CG models for glycerol to the weighting function employed for defining the local density. We employ the multiscale coarse-graining (MS-CG) method to simultaneously parameterize both pair and LD potentials. When employing a short-ranged Lucy function that defines the local density from the first solvation shell, the MS-CG model accurately reproduces the pair structure, pressure-density equation of state, and liquid-vapor interfacial profile of the AA model. The accuracy of the model generally decreases as the range of the Lucy function increases further. The MS-CG model provides similar accuracy when a smoothed Heaviside function is employed to define the local density from the first solvation shell. However, the model performs less well when this function acts on either longer or shorter length scales.

BOCS: Bottom-up Open-source Coarse-graining Software.

We present the BOCS toolkit as a suite of open source software tools for parametrizing bottom-up coarse-grained (CG) models to accurately reproduce structural and thermodynamic properties of high-resolution models. The BOCS toolkit complements available software packages by providing robust implementations of both the multiscale coarse-graining (MS-CG) force-matching method and also the generalized-Yvon-Born-Green (g-YBG) method. The g-YBG method allows one to analyze and to calculate MS-CG potentials in terms of structural correlations. Additionally, the BOCS toolkit implements an extended ensemble framework for optimizing the transferability of bottom-up potentials, as well as a self-consistent pressure-matching method for accurately modeling the pressure equation of state for homogeneous systems. We illustrate these capabilities by parametrizing transferable potentials for CG models that accurately model the structure, pressure, and compressibility of liquid alkane systems and by quantifying the role of many-body correlations in determining the calculated pair potential for a one-site CG model of liquid methanol.

Extending pressure-matching to inhomogeneous systems via local-density potentials.

Bottom-up coarse-grained models describe the intermolecular structure of all-atom (AA) models with desirable accuracy and efficiency. Unfortunately, structure-based models for liquids tend to dramatically overestimate the thermodynamic pressure and, consequently, tend to vaporize under ambient conditions. By employing a volume potential to introduce additional cohesion, self-consistent pressure-matching provides a simple and robust method for accurately reproducing the pressure equation of state (EoS) for homogeneous fluids, while still preserving an accurate description of intermolecular structure. Because they depend upon the global density, though, volume potentials cannot be directly employed for inhomogeneous systems, such as liquid-vapor interfaces. In the present work, we demonstrate that volume potentials can be readily adapted as potentials of the local density. The resulting local-density potentials provide an accurate description of the structure, pressure EoS, and local density fluctuations of an AA model for liquid methanol. Moreover, we demonstrate that very slight modifications to these local-density potentials allow for a quantitative description of either local or global density fluctuations. Most importantly, we demonstrate that the resulting potentials, which were parameterized to describe a homogeneous liquid, also generate stable liquid-vapor coexistence. However, further work is necessary to more accurately reproduce the interfacial density profile.

Trimethylamine N-oxide stabilizes proteins via a distinct mechanism compared with betaine and glycine.

We report experimental and computational studies investigating the effects of three osmolytes, trimethylamine N-oxide (TMAO), betaine, and glycine, on the hydrophobic collapse of an elastin-like polypeptide (ELP). All three osmolytes stabilize collapsed conformations of the ELP and reduce the lower critical solution temperature (LSCT) linearly with osmolyte concentration. As expected from conventional preferential solvation arguments, betaine and glycine both increase the surface tension at the air-water interface. TMAO, however, reduces the surface tension. Atomically detailed molecular dynamics (MD) simulations suggest that TMAO also slightly accumulates at the polymer-water interface, whereas glycine and betaine are strongly depleted. To investigate alternative mechanisms for osmolyte effects, we performed FTIR experiments that characterized the impact of each cosolvent on the bulk water structure. These experiments showed that TMAO red-shifts the OH stretch of the IR spectrum via a mechanism that was very sensitive to the protonation state of the NO moiety. Glycine also caused a red shift in the OH stretch region, whereas betaine minimally impacted this region. Thus, the effects of osmolytes on the OH spectrum appear uncorrelated with their effects upon hydrophobic collapse. Similarly, MD simulations suggested that TMAO disrupts the water structure to the least extent, whereas glycine exerts the greatest influence on the water structure. These results suggest that TMAO stabilizes collapsed conformations via a mechanism that is distinct from glycine and betaine. In particular, we propose that TMAO stabilizes proteins by acting as a surfactant for the heterogeneous surfaces of folded proteins.