(743i) Hydrophobic Association In a Spherically-Symmetric Water Model

A frequent route to simulating complex biomolecular systems is to employ coarse-grained models instead of all-atom ones, in turn allowing for longer and larger studies [1].  In particular for computational efficiency, a frequent coarse-graining target is the vastly abundant aqueous solvent in these systems.  Nevertheless, a critical issue in such approaches is the ability of coarse-grained models to adequately reproduce the relevant water-mediated driving forces, namely through correct reproduction of hydrophobic association [1]. 

In this work, we address the ability of pairwise coarse-grained isotropic water models in reproducing several signatures of hydrophobicity.  Such models are common in the literature, and here, we consider a particular family optimized to bulk water properties using the relative entropy approach, a new methodology that minimizes coarse-graining errors (e.g., by ensuring accurate reproduction of bulk water structural correlations) [2].  We show that such a simplified description effectively manifests water’s hydrogen bonding behavior, not necessarily by the form of the optimized potentials, but rather by their peculiar variation in state space.  These features in turn give rise to signatures of water’s unique thermophysical properties (temperature of maximum density, diffusivity increase upon compression, etc.) [2].  We also demonstrate that such models successfully explain many features of the hydrophobic force, by examining the association free energies of a pair of nonpolar solutes immersed in the coarse-grained solvent [3].  To perform this computation efficiently, we develop a new transition-matrix Monte Carlo approach that gives superb accuracy and precision in the potential of mean force curves [4].  By letting the nonpolar spheres vary in size, we examine the expected manifestation of the crossover in scaling (from volume to area) of hydrophobic association.  We also examine the ability of the model in replicating other aspects of hydrophobicity (e.g., its temperature behavior).  Nevertheless, some of our findings point to the fact that more detail may be necessary in the coarse-grained description (e.g., multi-body terms may complement the pairwise term in order to better capture water’s tetrahedral network of hydrogen bonds).

1.         Ayton, G.S., W.G. Noid, and G.A. Voth, Multiscale modeling of biomolecular systems: in serial and in parallel. Current Opinion in Structural Biology, 2007. 17(2): p. 192-198.

2.         Chaimovich, A. and M.S. Shell, Anomalous waterlike behavior in spherically-symmetric water models optimized with the relative entropy. Physical Chemistry Chemical Physics, 2009. 11(12): p. 1901-1915.

3.         Hammer, M.U., et al., The Search for the hydrophobic force law. Faraday Discussions, 2010. 146: p. 299-308.

4.         Shell, M.S., P.G. Debenedetti, and A.Z. Panagiotopoulos, An improved Monte Carlo method for direct calculation of the density of states. The Journal of Chemical Physics, 2003. 119(18): p. 9406-9411.