Equilibrium Properties and Force-Driven Unfolding Pathways of RNA Molecules

The mechanical unfolding of a simple RNA hairpin and of a 236-base portion of the Tetrahymena thermophila ribozyme is studied by means of an Ising-like model. Phase diagrams and free energy landscapes are computed exactly and suggest a simple two-state behavior for the hairpin and the presence of intermediate states for the ribozyme. Nonequilibrium simulations give the possible unfolding pathways for the ribozyme, and the dominant pathway corresponds to the experimentally observed one.

Figure 1

Force-Temperature phase diagrams of the 1EOR molecule. Left panel: average order parameter $⟨m⟩$. Right panel: average end-to-end length $⟨L⟩$.

Figure 2

Free energy landscape $F_0$ of the 1EOR molecule as a function of the molecular elongation $L$. Inset, tilted FEL $F_0-fL$, with $f=15.4\mathrm{pN}$.

Figure 3

Force-Temperature phase diagrams of the T. thermophila ribozyme. Left panel: average order parameter $⟨m⟩$. Right panel: average end-to-end length $⟨L⟩$.

Figure 4

Free energy landscape $F_0$ of the 1GRZ molecule as a function of the molecular elongation $L$, for $T=300\mathrm{K}$ (full line). Tilted FEL $F(L,f)$ for two values of the force $f=8.82\mathrm{pN}$ (dashed line) and $f=17.64\mathrm{pN}$ (dotted line, inset).

Figure 5

Typical unfolding trajectory of the 1GRZ molecule. (a) Force as a function of the position of the “optical trap” center $X$. (b) Order parameter of the whole system and of the single SSEs as functions of $X$.