PHYS 10 |
| The ability of single cell organisms to sense environmental stimuli is critical for their survival. Bacteria have evolved an effective system for sensing that is composed of two components, a sensing protein and response regulator protein. The sensing protein senses external stimuli and then propagates the signal through the membrane to the cytoplasmic portion where a cascade of events leads to the activation of a response regulator protein, and eventually genes able to properly respond to the extracellular stimuli. A mechanistic understanding of how two-component systems (TCS) work would allow the design of compounds that can disrupt the signaling cascade, and interfere with bacterial resistance mechanisms. In an effort to begin elucidating how the various stimuli are propagated through the membrane, we have constructed a three-dimensional model for the complete PhoQ (the sensor protein in the PhoQ/PhoP TCS involved in cation and cationic antimicrobial peptide sensing) using a two-step protocol. Structural homology modeling has been used to prepare a set of initial models, and a novel hybrid molecular mechanics/coarse grained dynamics scheme has been adopted to validate them. The sampling power of such a coarse grained approach is able to further refine the modeling, giving moreover mechanical insights into the signal transmission mechanism of PhoQ. |
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Structural Determination, Refinement, and Modeling of Large Biomolecular Complexes
8:00 AM-12:00 PM, Sunday, August 19, 2007 BCEC -- 157C, Oral
Division of Physical Chemistry |