A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces

Abstract

Significance As first proposed more than 200 y ago by Grotthuss, proton transport is enabled by a chemical bond-breaking and bond-making proton-hopping mechanism through water networks or “wires,” often contained within confined systems such as protein channels or nanotubes. Herein, concepts from graph theory are utilized in order to define a continuously differentiable collective variable for water wire connectivity and facile proton transport. As such, the water connectivity can be explicitly quantified via free-energy sampling to both qualitatively and quantitatively describe the thermodynamics and kinetics of water-facilitated proton transport via Grotthuss hopping—something that has been lacking since the first conceptual identification of this key chemical process in nature.