Using Metadynamics To Explore the Free Energy of Dewetting in Biologically Relevant Nanopores.

Water confined within hydrophobic spaces can undergo cooperative dewetting transitions due to slight changes in water density and pressure that push water toward the vapor phase. Many transmembrane protein ion channels contain nanoscale hydrophobic pores that could undergo dewetting transitions, sometimes blocking the flow of ions without physical blockages. Standard molecular dynamics simulations have been extensively applied to study the behavior of water in nanoscale pores, but the large free energy barriers of dewetting often prevent direct sampling of both wet and dry states and quantitative studies of the hydration thermodynamics of biologically relevant pores.