LAUSR

The ribosome is a large ribonucleoprotein complex that is responsible for translation of proteins in all living organisms. Accommodation is a key conformational change during transfer RNA (tRNA) selection that allows for each molecule to fully associate with the ribosome. During tRNA accommodation, there are large-scale fluctuations in the L11 stalk and the associated protein. Experimental and theoretical work has shown that the L11 protein and RNA exhibit dynamic behavior, where their precise position can significantly affect the dynamics of elongation. To explore the impact of L11 stalk mobility on the kinetics of aa-tRNA accommodation, we used molecular dynamics simulations with a simplified model to evaluate the free-energy as a function of aa-tRNA position. We find that as the flexibility of L11 is decreased, the position of the free-energy minima is robust. In contrast, the magnitude of the free-energy barrier for accommodation depends on the precise scale of L11 fluctuations. We find that increasing the rigidity of the L11 stalk can destabilize the A/T ensemble. In addition to the close relationship between L11 mobility and the free-energy landscape of accommodation, the direction of L11 stalk movement is also correlated with aa-tRNA displacements. To probe the collective motion of the L11 stalk, we performed Principal Component Analysis on the simulated trajectories. When aa-tRNA is first delivered to the ribosome, the stalk moves away from the tRNA and adopts extended configurations. It then relaxes during the accommodation process. Together, these calculations reveal a correlation between fluctuations in the L11 stalk and the dynamics of aa-tRNA during accommodation. This provides a quantitative foundation for interpreting experimental measures of accommodation and suggests how the dynamics of the L11 stalk may contribute to aa-tRNA proof-reading and accommodation.