This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
A great challenge facing today's post-genomic era is how to understand the hidden information buried within genomes. A crucial step in information decoding from DNA sequence to protein structure occurs through the function of the ribonucleic acid (RNA) molecules. The functions of RNA depend on the three-dimensional structure and stability. Because RNAs are highly charged polyanions, their folding concentrates negative charge, which is countered by significant ion binding to the RNA making structure and stability strongly dependent on ion effects in the solution. Many modeling studies on the ion effects in RNA folding are based on the mean-field Poisson-Boltzmann approaches. These approaches do not consider correlations, fluctuations or finite size of the ions. However, a variety of experiments have pointed to the potential importance of these three effects for multivalent ions such as magnesium. Because magnesium ions are essential for RNA tertiary structure folding, the inability to treat the correlation/fluctuation and ion size effects has greatly limited the understanding, prediction, and design RNAs in various applications. This project will address this deficiency in theory by developing a new model for understanding the to role of divalent ions on the RNA structure and function.
Broader impacts: Quantitative predictions for the ion effects in RNA folding will impact a broad range of RNA-related research, including quantification of the stabilizing forces in RNA, prediction of RNA stability and folding cooperativity, quantitative understanding of the mechanisms of ribozymes, riboswitches and microRNAs, and rational design of therapeutic RNA aptamers. The project will provide unique educational and training opportunities for graduate and post doctoral student coming from traditional physical science backgrounds and allow them to move into the field of biophysics.
