(717h) Characterizing Water Density Fluctuations to Accurately Estimate Hydrophobic Interactions

Predicting the thermodynamics of molecular interactions remains a difficult challenge at the forefront of molecular-scale science. While the direct interactions between binding partners can be characterized with relative ease, solvent-mediated interactions are often more complex. Recent work has uncovered that the relative hydrophobicity of nanoscale surfaces can be characterized by the ease with which a cavity can be created in its vicinity, such that cavities form more readily at hydrophobic surfaces. This behavior is a direct manifestation of an enhancement of water density fluctuations near hydrophobic materials. We exploit a detailed understanding of these density fluctuations in uniform and non-uniform environments to better understand and even predict the thermodynamics of hydrophobic interactions. Our findings suggest novel strategies for accurately quantifying the hydration contribution to the thermodynamics of biomolecular binding processes.