INDUSTRY

Previously, University of Chicago's Benoit Roux set out to explain how fast ion conduction could take place at a rate near the diffusion limit through the channel and yet maintain a robust ion selectivity. The results of this work were reported in a 2004 issue of Nature. More recently, Roux and his collaborators have been exploring the molecular basis for the activation of these ion channels in response to changes in membrane electrostatic potential, that is, the opening of the portals. This process, referred to as "gating," takes place on a microsecond timescale. In a 2005 issue of Nature, the team proposed a gating mechanism based on the experimental observation that the transmembrane electric field is actually focused at the charged arginine residues part of the "voltage-sensor" of the channel. It surmises that the arginines do not translocate across the membrane and that the voltage-sensor functions much as a "membrane transporter." Model of voltage-sensor configuration a potassium channel in the closed state, overlaid with the transmembrane electrostatic potential surface. Image courtesy of Benoit Roux, University of Chicago. The team uses molecular dynamics simulations on NCSA's Tungsten computing cluster to develop their theories about the function of potassium channels. They also compute at NCSA's sister site, the Pittsburgh Supercomputing Center. They are currently designing suitable computational strategies that will enable them to observe channel gating through these simulations, based on experimentally obtained views of the channel. "Although the experimentally determined three-dimensional structure of membrane channels yields a wealth of information," Roux says, "the function of these membrane channels is intrinsically dynamical. Theoretical considerations are absolutely necessary for understanding the underlying mechanisms of selective ion conduction and gating."