Because of the potential link between -1 programmed ribosomal frameshifting (PRF) and response of a pseudoknot (PK) RNA to force, a number of single molecule pulling experiments have been performed on PKs to decipher the mechanism of PRF . Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying f and C, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As f and C are changed, the stem-loop tertiary interactions rupture first  followed by unfolding of the 3^{\prime}-end hairpin (I\rightleftharpoonsF). Finally, the 5^{\prime}-end hairpin unravels producing a extended state (E\rightleftharpoonsI). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as \left(\log C_{m}\right)^{\alpha} with \alpha=1\,(0.5) for E\rightleftharpoonsI (I\rightleftharpoonsF) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single molecule experiments, as done previously for DNA hairpins. A by product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5^{\prime}-end hairpin that the ribosome first encounters during translation.
Because of the potential link between -1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting . Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying f and C, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As f and C are changed, the stem-loop tertiary interactions rupture first , followed by unfolding of the 3^{\prime}-end hairpin (I\rightleftharpoonsF). Finally, the 5^{\prime}-end hairpin unravels , producing an extended state (E\rightleftharpoonsI). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as \left(\log C_{m}\right)^{\alpha} with \alpha=1\,(0.5) for E\rightleftharpoonsI (I\rightleftharpoonsF) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5^{\prime}-end hairpin that the ribosome first encounters during translation.
D
(PRF)
R
PRF
programmed ribosomal frameshifting
A
,
R
producing a
, producing an
R
single molecule
single-molecule
R
by product
by-product