Quantifying Collective Dynamics in the Ribosome

The functional dynamics of molecular assemblies often involve large-scale collective rearrangements. While these motions occur in a high-dimensional space, experiments are typically only able to simultaneously measure a small number of interatomic distances. Accordingly, a major challenge in single-molecule studies is to identify kinetically-relevant degrees of freedom. To address this issue for the ribosome, we use a range of theoretical models and molecular dynamics simulations in order to simulate hundreds of spontaneous large-scale (~30-50 Å) conformational transitions at various points of the elongation cycle. With these large data sets, we are assessing the ability of experimentally-accessible coordinates to capture the rate-limiting free-energy barriers. This analysis suggests design strategies for next-general experiments, as well as helps rationalize controversial/contradictory experimental observations. Finally, these calculations provide a quantitative foundation that is allowing us to study the precise relationship between structure and dynamics in the ribosome.