(446b) Novel Theoretical and Simulation Techniques to Quantify the Hydrophobic Effect

Hydrophobic hydration and hydrophobically-driven assembly play a central role in biology. Recent work has shown that the local water density fluctuations (and not the mean water density), at a solid-water surface, are a robust measure of it’s hydrophobicity. These fluctuations can be quantified by calculating the probability, P(N), of observing N waters in an observation volume (e.g., the hydration shell of a protein) of interest, v. When v is large, calculating P(N) using molecular dynamics simulations is challenging, as the probability of observing very few waters is exponentially small, and the standard procedure for overcoming this problem (umbrella sampling in N leads to undesirable impulsive forces. We have recently developed an indirect umbrella sampling (INDUS) method, that samples a coarse-grained particle number to obtain P(N) in volumes of all shapes and sizes, in a variety of environments, and all thermodynamic conditions. The INDUS method will be of particular interest in characterizing the hydrophobicity of interfaces of proteins, nanotubes and related systems. We have also implemented the ideas underlying the Lum-Chandler-Weeks theory of hydrophobicity into a lattice-based model that is in reasonable quantitative agreement with simulations results, with a 2 to 3 orders of magnitude improvement in computational efficiency.