Physical principles governing ribosome free-energy landscape: from elongation to rescue.

Ribosomes undergo large-scale conformational changes governed by steric, entropic, and electrostatic factors. Using all-atom structure-based models (SMOG), we investigate how these factors shape ribosome dynamics in eukaryotic and bacterial systems. To capture ionic effects on RNA structure and dynamics, we developed a model that accurately reproduces ionic environment and chelated ion positions in benchmark RNA systems. Applying this to yeast ribosomes, we demonstrate how ionic concentration modulates the free-energy landscape of subunit rotation and identify concentration-sensitive residues at the intersubunit interface. We extend our framework to bacterial trans-translation, where tmRNA and SmpB rescue stalled ribosomes. We model translocation of the tmRNA-SmpB complex as it moves through ribosomal A, P, and E sites, exploring how steric factors influence this rescue pathway. These studies establish a computational framework for understanding physical principles governing ribosome function across biological contexts, with implications for translation mechanisms and therapeutic development.