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Ribozymes are molecules of RNA that act as catalysts to speed up chemical reactions in the body by factors up to 10 million. The classical central dogma of molecular biology confines the role of RNA to be that of a molecular messenger carrying genetic information transcribed from DNA in the cell's nucleus into the cytoplasm where it would be translated into protein gene products. This hypothesis was shattered with the discovery in 1982 that RNA could act as a catalyst - a breakthrough that has since resulted in two Nobel prizes, given birth to the fields of ribozyme engineering, and shaped the foundations of new theories of how life itself originated. However, despite the tremendous importance of RNA catalysis in biology, biomedicine and evolution - scientists have yet to unveil the chemical origins of their unique catalytic capability.
The projects available in the York Lab (http://theory.rutgers.edu/) involve the study of the chemical mechanisms of these amazing RNA enzymes using state-of-the-art molecular simulation tools. These tools allow one to characterize and understand - at the atomic level - the structure and dynamics of the RNA molecules in solution, and the detailed catalytic pathways that enable their incredible rate enhancements. The simulation results will allow scientist to watch the chemical reaction taking place as a 3D movie in full atomistic detail, and in some cases interact with the molecules in a virtual reality environment.
Very recently there have been breakthroughs in the discovery of 4 new classes of ribozymes, and their structural characterization by X-ray crystallography. These structures provide a key departure point for several inter-related undergraduate projects that aim to bridge the gap between structural and mechanistic measurements, and provide a detailed dynamical picture of mechanism at atomic-level resolution. In this way, molecular simulations have the potential to unify the interpretations of a broad range of experimental data and establish a consensus view of mechanism. Ultimately, molecular simulations provide predictive insight into catalysis, including control factors that regulate selectivity and reactivity, and uncover general principles that may guide rational design effort.
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