Ribosomes undergo large-scale conformational changes that are central to protein synthesis, and understanding the underlying physico-chemical properties is key to connecting molecular structure with function. Using all-atom structure-based models (SMOG), we investigate how steric, entropic, and electrostatic factors govern ribosome dynamics in bacterial and eukaryotic systems. In yeast ribosomes, we focus on how ionic concentration modulates the free-energy landscape of subunit rotation, providing insight into the physical principles that control elongation. While these models have elucidated key mechanistic features of elongation, the dynamics of trans-translation remain elusive. In bacteria, trans-translation rescues stalled ribosomes via transfer-messenger RNA (tmRNA) and its protein partner SmpB, which release stalled ribosomes, tag incomplete polypeptides, and allow translation to resume. We study the translocation of the tmRNA-SmpB complex, including the tRNA-like domain (TLD), mRNA-like domain (MLD), and SmpB, as it moves through the ribosomal A, P, and E sites. This simplified model provides an all-atom description of the system, enabling efficient exploration of large-scale conformational pathways. These studies reveal how the interplay of physical and chemical factors shapes ribosome dynamics, from elongation in yeast to trans-translocation in bacterial rescue. Our work establishes a computational framework for dissecting fundamental aspects of translation and highlights potential strategies for modulating ribosome function in the context of antibiotic development.
Wanes et al. (Sun,) studied this question.