Force-induced denaturation of RNA

We quantitatively describe an RNA molecule under the influence of an extern al force exerted at its two ends as in a typical single-molecule experiment . Our calculation incorporates the interactions between nucleotides by usin g the experimentally determined free energy rules for RNA secondary structu re and models the polymeric properties of the exterior single-stranded regi ons explicitly as elastic freely jointed chains. We find that despite compl icated secondary structures, force-extension curves are typically smooth in quasi-equilibrium. We identify and characterize two sequence/structure-dep endent mechanisms that, in addition to the sequence-independent entropic el asticity of the exterior single-stranded regions, are responsible for the s moothness. These involve compensation between different structural elements on which the external force acts simultaneously and contribution of subopt imal structures, respectively. We estimate how many features a force-extens ion curve recorded in nonequilibrium, where the pulling proceeds faster tha n rearrangements in the secondary structure of the molecule, could show in principle. Our software is available to the public through an "RNA-pulling server."