Abstract
Protein synthesis in the cell is controlled by an elaborate sequence of conformational rearrangements in the ribosome. The composition of a ribosome varies by species, though they typically contain ∼ 50-100 RNA and protein molecules. While advances in structural techniques have revolutionized our understanding of long-lived conformational states, a vast range of transiently visited configurations can not be directly observed. In these cases, computational/simulation methods can be used to understand the mechanical properties of the ribosome. Insights from these approaches can then help guide next-generation experimental measurements. In this short review, we discuss theoretical strategies that have been deployed to quantitatively describe the energetics of collective rearrangements in the ribosome. We focus on efforts to probe large-scale subunit rotation events, which involve the coordinated displacement of large numbers of atoms (tens of thousands). These investigations are revealing how the molecular structure of the ribosome encodes the mechanical properties that control large-scale dynamics.