In an ongoing collaboration with University of Minnesota researchers Betsy Kren and Clifford Steer, this research sought to determine the three-dimensional structure of a chimeraplast molecule. These RNA:DNA hybrids are gene therapy's newest "magic bullet," allowing direct correction of single site mutational events in higher organisms. The computers and programs of the BSCL facility have been crucial in analysis of the two physical structure approaches being pursued: small molecule X-ray crystallography of a whole chimeraplast, and nuclear magnetic resonance (NMR) structural studies of model compounds containing key structural features. The NMR approach was combined with a direct modeling approach in order to elucidate the structure of these molecules in solution to aid in better design of chimeraplasts directed toward different targets.

  During the past six months, Dr. Eccleston used the BSCL computers to build the structure program nab and the NMR program morass for use on this project and have worked on several model structures. He is currently using the program amber for molecular dynamics and energy minimization as well as for counterion addition and buffer ionic strength simulation using the Point Mesh Ewald capabilities of the program following the amber tutorial by Thomas Cheatham. As a consequence of the Supercomputing InstituteÕs sponsorship of the CHARMm tutorials in the fall of 1999, Dr. Eccleston obtained an academic license for CHARMm and intended to use it for additional modeling of chimeraplasts (particularly for the unusual 2'-O-Methyl RNA derivatives in these molecules for which there is little direct structural data).