Resolution-exchanged simulations reveal ribosomal frameshifting via subunit rolling. Chang et al.

We are interested in modeling the perturbed dynamics of the ribosome upon encountering a stable mRNA pseudoknot (human telomerase dU177 variant), and how the resulting conformational changes lead to programmed ribosomal frameshifting. First, all of the missing subunits of the non-rotated- and rotated-state ribosomes were modeled (provided here as PDB files). The intrinsic dynamics of these ribosome structures were obtained with anisotropic network model (ANM; codes available on https://github.com/Yuan-Yu/bioStructureM). Second, the pseudoknot structure was pulled into the mRNA entrance of the ribosome with steered molecular dynamics (SMD) simulations (trajectory provided here). The interaction forces between the pseudoknot and the mRNA entrance were calculated from SMD simulations, and combined with intrinsic dynamics from ANM using linear response theory (LRT; codes available on https://github.com/Yuan-Yu/bioStructureM). Interestingly, a rolling motion of 30S was observed. Finally, the tRNAs and their surroundings of the rolled structure were equilibrated with MD simulations. After equilibration, production runs of MD simulations revealed spontaneous tRNA slippage (trajectory provided here), indicating that pseudoknot-induced subunit rolling is the motion that triggers programmed ribosomal frameshifting.