Modeling RNA: from small molecules to bacterial polysomes

Ribonucleic acids (RNAs) are biomolecules involved in a variety of cellular processes facilitated by the ability to adopt diverse structures with unique functions. In many instances, studying RNA structure-function relationships through experimental techniques is an arduous process. By contrast, computer simulations can model RNA behavior at levels of detail that are difficult to observe or inaccessible in experiment. The utility of simulations relies on accurate energy functions used to describe molecular behavior, referred to as “force fields.” In the first part of my thesis, I show deficiencies in current RNA force fields that I correct by modifying parameters describing how atoms interact to match experimental data and apply these modified parameters to a range of RNA systems. Importantly, the modified parameters did not “break” the original force field and improved the simulated behavior of RNAs that were not used to match experiment, suggesting that they may be transferrable to RNAs that were not studied. When attempting to model thousands of large RNAs present in the cell with atomic detail, many computational techniques are either too slow or inaccurate. Therefore, the second part of my thesis, describes the development of RNA modeling techniques that can be applied to build large RNAs composed of thousands of atoms. I use this technique to build models of bacterial polyribosomes – the machinery that translates the genetic code into proteins – as well as other molecules necessary for translation. The models provide a starting point for future simulations and suggest possible relationships between structure and biological function.