To address these limitations, Tajkhorshid and graduate student James Gumbart used two software programs developed in the U. of I.s National Institutes of Health Resource for Macromolecular Modeling and Bioinformatics. The programs, NAMD and VMD, respectively, simulate and visualize complex molecular interactions. By entering detailed data about the position and characteristics of every atom in the system, the researchers ran simulations of various scenarios to test which hypotheses were most feasible. Their work relied on detailed crystallographic studies of the molecules provided by University of Virginia researcher Michael C. Wiener.
The good thing about simulations is that you can monitor the position of every atom, Tajkhorshid said.
The task was enormous, however.
The fundamental motions of atoms that guide large conformational changes happen on a very short time scale: femtoseconds, Tajkhorshid said. Each step relies on the completion of a previous step, so the simulations take an extensive amount of time and considerable computational effort.
The researchers addressed two key questions: First, could the bond between TonB and the luminal domain withstand the force needed to pull the luminal domain downward, away from the barrel" Second, how does the luminal domain respond to force in order to expose a permeation pathway through the barrel"
In the first simulation the researchers applied a force to TonB and showed that the multiple hydrogen bonds between TonB and the luminal domain were strong enough to remain intact while TonB pulled the end of the luminal domain away from the barrel. The simulation also showed the luminal domain gradually unfolding,
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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
5-Jun-2007