Dependence of P/E tRNA hybrid formation on subunit rotation in the ribosome

The ribosome, a massive two-subunit nucleoprotein assembly, is responsible for protein synthesis in all living cells. During the protein elongation cycle, the ribosome and tRNA molecules undergo several large-scale functional rearrangements. This study explores two such rearrangements during the bacterial translocation step: P/E tRNA hybrid formation and inter-subunit rotation. We employ multi-basin all-atom structure-based (SMOG) models and the Ribosome Angle Decomposition (RAD) method to investigate the dependence of P/E hybrid formation on small subunit body rotation relative to the large subunit. Structure-based models provide a simplified energetic description, where experimental structures are defined to be the potential energy minima. Using all-atom structure-based models, we simulate spontaneous P/E hybrid formation. By analyzing tRNA dynamics at various degrees of small subunit body rotation, we elucidate the precise physical relationship between these two large-scale collective processes. Our results reveal a non-monotonic dependence of mean first passage time (mfpt) for P/E hybrid formation on subunit rotation. Specifically, the mfpt for P/E hybrid formation decreases as body rotation increases to a threshold value, beyond which it increases. The all-atom SMOG model provides insights into the structural factors governing these dynamics, including the identification of individual proteins that introduce sterically-induced barriers leading to this non-monotonic behavior.