The TraDES (Trajectory Directed Ensemble Sampling) approach, developed in the Hogue laboratory, has been shown by NMR spectroscopists to be well suited for sampling non-globular protein conformational space.  TraDES was awarded US Patent No. 6490532.

We have identified a number of opportunities in the field of computer simulation to characterize the structure-function relationship of a large set of proteins which have been refractory to structural studies.  These include proteins that refuse to crystallize, such as a number of proteins with large non-globular domains of Pro rich composition, including N-WASP, p130Cas, formins and the ACTA protein of Listeria monocytogenes.

We are adapting the TraDES software to scan non-globular protein domains and analyze their compatibility with the 3D structures of target binding proteins, as well as kinases and phosphatases. This will yield a conformational sampling approach, with statistics of the sub-population of conformations that bind to varying numbers of protein ligands or enzymes.  We hope this approach will yield insight into potential conformational changes and regulatory mechanisms that were previously undetected, but hinted at in a number of in-vivo experiments.