RNA is a molecular machine that carries out a large number of tasks within the cell. The awareness of its central involvement in biological processes is among the most remarkable scientific discoveries of the last thirty years. In the earliest models, RNA's role was relegated to that of messenger, passively copying and transporting pieces of the genetic code. Recent research illustrates its active participation in executing the instructions present in the genome. RNA's widely-varying functions range from 'splicing' genes together to regulating the concentrations of key metabolites. Many of these newly discovered roles rely on RNA folding to specific functional structures and responding to the environment by dynamically changing shape. The goal of this proposal is to obtain an atomically detailed picture of the RNA folding process. This vision is beyond current experimental capabilities, but is on the horizon for new simulation methods. However, simulation must be validated by observation. This project identifies important landmarks along the folding pathway of a small RNA that can be detected with advanced experimental tools. Observation of the time scale for and sequences of events will be determined by experiment, and used to validate simulations, which provide insight into atomically detailed processes. The expanding appreciation of RNA's biological roles brings recognition of its potential as a new target for drugs. Insights gained int the atomic level workings of RNA folding and dynamics may assist with RNA based drug design.
The need for new antibiotics cannot be overstated as bacteria continue to acquire antibiotic resistance. Efforts are intensifying to develop drugs that specifically target bacterial RNAs. However, a lack of detailed understanding regarding small molecule binding by RNA limits drug development and will be facilitated by insights gained here into atomically detailed motions of RNA.
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