Molecular dynamics (MD) has become an essential tool for obtaining microscopic insight into biological function. The gramicidin channel as an excellent benchmark system for this purpose. Using extensive MD simulations with explicit solvent and membrane, we determine the backbone structure and side-chain rotameric states compliant with solid-state Nuclear Magnetic Resonance and fluorescence spectroscopic observations. Such agreement is not possible without dynamical simulation and underscores the utility of MD for the analysis and interpretation of experimental observations. Ion conduction through the gramicidin channel is then characterized with free energy simulation techniques. We determine the roles played by protein, water and membrane in creating a free energy pathway for ions. This breakdown reveals the striking ability of single-file water to stabilize an ion within the narrow channel, and the importance of the electric dipole of this water to the ion permeation process. An important strength of the present free energy strategy is to help provide a rigorous conceptual framework to characterize the mechanism of ion conduction at the microscopic level.
PHYS 242, Purdue University, West Lafayette, IN