SC2001 Demonstrations

"If I could just get my hands on that protein!" Single molecule manipulation techniques like atomic force microscopy have brought us closer to this frequently expressed wish. These techniques, however, do not "see" the atomic level detail needed to relate mechanism to protein architectures. True, computational methods do illuminate the elusive protein structures, but are limited to static structures, or trajectories yielded by weeks-long simulations. Now, with the advent of high-performance computing, interactive manipulation of molecular dynamics simulations has become a reality. Linking advanced molecular graphics with ongoing molecular dynamics simulations, and utilizing a haptic device to connect forces from a user's hand with forces in the simulation, researchers can interact with "live" proteins. The new methodology is described in a recent publication and the figure shown here demonstrates a Cl^- ion being pulled through a gramicidin A channel (see a 3.8mb Streaming Video).

"How do you feel?" Biologists now have an answer that may surprise you. Our sense of touch relies upon the fact that cells in our fingertips can sense the pressure from a tabletop and transmit a signal to the brain. But until recently, the molecular mechanism for turning the stretching of a cell membrane into a cellular signal was unknown. An important step in understanding this process was the discovery of a protein known as a the mechanosensitive channel of large conductance, or MscL. Though this protein has been studied primarily in bacteria, homologues exist in all major kingdoms of life. Researchers in the Theoretical Biophysics Group have used molecular dynamics simulations to study, at the atomic level, how MscL opens in response to pressure changes. Models of MscL will give us new insight, not only into how we feel, but also how our hearts beat and how we keep our balance. Feel better now? (more, publication)

This is a simulation of a model of MscL from E. coli provided by our collaborators S. Sukharev and R. Guy from the U. of Maryland and the NIH, respectively. The SMD simulation is designed to test a proposed model of MscL gating.

Aquaporins make up an important family of proteins that allow water to pass through cell membranes, while blocking undesired ions and larger molecules. At least eleven different types of aquaporins can be found in the human body, and their malfunction may be linked to common diseases. Some of the aquaporins serve a double-purpose: they also allow the movement of one or more other specific molecules into and out of cells.

This is a simulation of GlpF, a typical aquaporin that also conducts glycerol (a simple sugar), but lets almost nothing else through. A molecule of glycerol is being pulled through the channel, allowing us to see the path that it follows. By studying simulations of this channel, TBG researchers are learning where this channel gets its amazing filtering ability.