Title: Dual Scale Modeling of RNA
Speaker: David Mathews, University of Rochester Medical Center, Department of Biochemistry & Biophysics and Biostatistics & Computational Biology
Abstract Recent discoveries have demonstrated that RNA serves many important cellular functions that were previously unknown. For example, it is RNA in the ribosome that catalyzes peptide bond formation and RNA is important in post-transcription gene regulation through RNAi. Given the recent awareness that RNA serves many important, previously unknown functions, there is interest in the discovery of novel functional RNA sequences, called non-coding RNA (ncRNA), in genomes. On the basis of predicted secondary structure formation free energy change, we have developed a sensitive and specific method for ncRNA discovery in crudely aligned genomes. For RNA to function, structures must be flexible. Conformational changes have been shown to be important for ribosome function and for RNA self-splicing. We have implemented the nudged elastic band (NEB) methodology in the AMBER molecular dynamics software package to determine low energy pathways for conformational changes. NEB can be used to quantitatively determine pathways of any timescale. We have modeled the conformation change of a GG non-canonical pair. Our results demonstrate the plasticity of RNA helices and that NEB can be used to find complex pathways for conformational changes.