Computer Simulations of Membrane Water Channels and Ion Channels

My talk will start with a brief general introduction of protein structures, and will then focus on membrane channel proteins, which selectively conduct specific molecules across the cell membrane, and play important roles in biology. The first part of the talk involves aquaporins, a family of membrane proteins that function as water channels. My focus is to calculate the major experimental observable, the osmotic permeability of water channels, from molecular dynamics (MD) simulations. For this purpose I established two solutions, a non-equilibrium simulation technique, and a collective diffusion model. Both methods have been applied in the studies of aquaporins as well as many other channels. In the second part of the talk, I will present my ongoing research on pentameric ligand-gated ions channels, which assume either an open or a closed conformation depending on external conditions, and play key roles in the transduction of nerve signals. I carried out MD simulations on both conformations of the protein, and identified a "hydrophobic gate" in the transmembrane pore as the major barrier for water and ion conduction. Adopting a multiscale approach, I also studied the conformational transition of the protein between the two states, and characterized the energetics of the transition pathway. These applications demonstrate that MD simulations, in combination with statistical mechanics, can provide important insight on the molecular mechanism of proteins.