Seminar Title: "Predicting RNA Structure with Physics and Sequence Comparison"

Abstract: RNA structure is hierarchical. The primary structure is the sequence of nucleotides. The secondary structure is the set of canonical (AU, GC, and GU) base pairs. The tertiary structure is the three dimensional position of the atoms and the additional intramolecular contacts that mediate the fold.

The Mathews lab develops methods to predict both RNA secondary structure and tertiary structure. In this talk, I will introduce nearest neighbor parameters for estimating folding stability of secondary structures and dynamic programming algorithms that predict secondary structure. I will then talk about new work in our lab to compare sequences to model conserved secondary structures. We developed a new method, called TurboFold, which is able to rapidly refine predicted secondary structures using sequence comparison and rapidly refine sequence alignments using structure information. I will also talk about new work to model RNA folding stability using molecular mechanics and 3D models. We used umbrella sampling to estimate the unfolding free energy change differences for three stem-loop structures, and we found good agreement with experiments.