A Coarse-Grained Simulation Study of Ribosome and tRNA Dynamics during Translocation

Abstract

In the final step of the translation-elongation cycle, the complex of two tRNA and mRNA molecules need to be advanced by exactly one codon in the ribosome. To realize this movement, the two ribosomal subunits are thought to be largely rearranged by the so-called ratchet-like rotation. This dynamic behavior, known as translocation, is essential for the efficient and accurate translation. Although many experiments, including high-resolution structural studies, have been performed, the mechanism of this movement is still unclear. Molecular dynamics simulation is a good tool to investigate such biological phenomena with atomic resolution. To overcome the limitations of system size and long-time scales, we have developed a coarse-grained (CG) simulation model of RNA and RNA-protein complexes. In this model, each nucleotide is represented as three CG beads and interactions are modeled with a structure-based potential, the parameters of which were determined by a fluctuation matching method to achieve higher accuracy. Next we employed this CG model to study the dynamic behavior of a ribosome complex. In particular, we focused on the relationship among the inter-subunit motion, fluctuation of the tRNAs in the binding sites, and tRNA-mRNA movement. The inter-subunit rotation is reproduced well by using two reference structures which correspond to the unrotated and fully-rotated state of the ribosome. Some experiments have suggested that tRNAs form hybrid states during the translocation phase, and we were motivated to examine whether or not this occurs in our CG simulations.