Mechanical properties of nucleic acids and the non-local twistable wormlike chain model

Abstract

We investigate the mechanical properties of double stranded RNA by means of all-atom simulations and compare its elastic behavior to that of DNA. Differently from DNA, which is characterized by a strong coupling between twist and roll degrees of freedom, such coupling is very weak in RNA. Both nucleic acids are characterized by couplings between distal sites, i.e.\ by interactions that go beyond nearest neighbors. These non-local couplings, both in RNA and DNA, are strong for tilt and twist degrees of freedom and weak for roll. We introduce and analyze a simple double stranded polymer model which clarifies the origin of the distal couplings. Overall, our results indicate that nucleic acid mechanics is well-described by a non-local Twistable Worm Like Chain (nlTWLC). Differently from its local counterpart, the nlTWLC is characterized by a length-scale-dependent elasticity: nucleic acids are mechanically softer at the scale of a few base pairs as compared to an asymptotic stiffer behavior.

Rigid Base Biasing in Molecular Dynamics Enables Enhanced Sampling of DNA Conformations

“…We note that the perturbation produces an oscillating decay of the twist. This is in line with the predictions of nonlocal models of DNA and dsRNA elasticity. , This behavior can be understood by a minimal (homogeneous) model of twist free energy E twist of the following type E twist = 1 2 ∑ n false[ C̃ normalΩ 3 2 ( n ) + C̃ ′ normalΩ 3 ( n ) normalΩ 3 ( n + 1 ) false] where the sum runs through all the sites and C̃ and C̃ ′ are the on-site and next-neighbor twist–twist couplings and Ω 3 ( n ) is the excess twist at site n . For simplicity we have limited the off-site interactions to a coupling between consecutive sites n and n ± 1, but this argument can be easily extended to interactions coupling more distant sites, as n and n + 2, etc .…”

“…1,2,37 A recent analysis quantified these nonlocal couplings for tilt, roll, and twist for both DNA 38 and dsRNA. 39 Very similar couplings were found in these two molecules. 39 Here we analyze structural deformations along the whole sequence of a DD dodecamer induced by local perturbations at a specific site.…”

“…Several studies have observed correlations between rigid base coordinates separated by a few nucleotides along the sequence, indicating the existence of couplings between distal sites. ,, A recent analysis quantified these nonlocal couplings for tilt, roll, and twist for both DNA and dsRNA . Very similar couplings were found in these two molecules .…”

“…For simplicity we have limited the off-site interactions to a coupling between consecutive sites n and n ± 1, but this argument can be easily extended to interactions coupling more distant sites, as n and n + 2, etc . Prior work showed that both DNA and dsRNA are characterized by C̃ ′ > 0 , while stability requires that C̃ > 0. Let us consider a perturbation of type enforcing ⟨Ω 3 ( k )⟩ > 0 at a given site k .…”

“…(b) Average excess buckle induced by a constraint of type applied to the second G nucleotide from the left. (c) Average decays of twist and buckle from MD simulations (symbols) and predictions from the continuum nonlocal twistable wormlike chain model. , We have explicitly added to the data points the error on the mean, defined as σ / M , with σ the standard deviation and M the number of independent samples. For most of the data, this is smaller than symbol sizes.…”