Sitting at the edge: How biomolecules use hydrophobicity to tune their interactions and function

Water near hydrophobic surfaces is like that at a liquid-vapor interface, where fluc-tuations in water density are substantially enhanced compared to that in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Conse-quently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance towards or away from the wet state, and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not. Much of biology happens in aqueous environments, with interfaces of biomolecules being wet [1,2]. Yet, hydrophobically driven assembly leads to contact surfaces that contain little or no water [3,4]. How biomolecules are able to perform the task of removing water from their vicinity is an important open question [5]. Here, we show that the answer lies in the proximit