Slowdown of Interhelical Motions Induces a Glass Transition in RNA

Abstract

RNA function depends crucially on the details of its dynamics. The simplest RNA dynamical unit is a two-way interhelical junction. Here, for such a unit--the transactivation response RNA element--we present evidence from molecular dynamics simulations, supported by nuclear magnetic resonance relaxation experiments, for a dynamical transition near 230 K. This glass transition arises from the freezing out of collective interhelical motional modes. The motions, resolved with site-specificity, are dynamically heterogeneous and exhibit non-Arrhenius relaxation. The microscopic origin of the glass transition is a low-dimensional, slow manifold consisting largely of the Euler angles describing interhelical reorientation. Principal component analysis over a range of temperatures covering the glass transition shows that the abrupt slowdown of motion finds its explanation in a localization transition that traps probability density into several disconnected conformational pools over the low-dimensional energy landscape. Upon temperature increase, the probability density pools then flood a larger basin, akin to a lakes-to-sea transition. Simulations on transactivation response RNA are also used to backcalculate inelastic neutron scattering data that match previous inelastic neutron scattering measurements on larger and more complex RNA structures and which, upon normalization, give temperature-dependent fluctuation profiles that overlap onto a glass transition curve that is quasi-universal over a range of systems and techniques.

Hierarchical Hydration Dynamics of RNA with Nano-Water-Pool at Its Core

“…However, we have calculated the local translational and reorientational dynamics of SAM-I RNA and water molecules: (i) for translational dynamics, we estimated the positional autocorrelation (Figure S20) between local structural trapped water molecule of SAM-I as indexed A as indicated in Figure b and its interacting RNA atoms, (ii) and in the case of reorientational relaxation, we compare the single-bonded N–H and P–O dipole vector’s (N–H and P–O bonds of the peripheral residues 59–65, 86–88 of SAM-I core) reorientational relaxation with the core–shell (0–5 Å) water molecules relaxation kinetics (see Table , Figure S21a,b and Table S8 in the Supporting Information), which evidently show that the slowest time component (τ 1 ) of water relaxation and structural reorientational relaxation of RNA (N–H and P–O bond vectors) are dynamically coupled (∼ns). The time scale is comparable with that observed in the NMR experiment …”

“…However, we have calculated the local translational and reorientational dynamics of SAM-I RNA and water molecules: (i) for translational dynamics, we estimated the positional autocorrelation (Figure S20) between local structural trapped water molecule of SAM-I as indexed A as indicated in Figure b and its interacting RNA atoms, (ii) and in the case of reorientational relaxation, we compare the single-bonded N–H and P–O dipole vector’s (N–H and P–O bonds of the peripheral residues 59–65, 86–88 of SAM-I core) reorientational relaxation with the core–shell (0–5 Å) water molecules relaxation kinetics (see Table , Figure S21a,b and Table S8 in the Supporting Information), which evidently show that the slowest time component (τ 1 ) of water relaxation and structural reorientational relaxation of RNA (N–H and P–O bond vectors) are dynamically coupled (∼ns). The time scale is comparable with that observed in the NMR experiment We have also investigated the correlation between the functional dynamics of kink-turn (KT) and core regions with the hydration dynamics in connection with the experimental results as summarized below: (a) Role of site-specific water controlling kink-turn dynamics: Early experiments proposed an ion environment-dependent conformational fluctuation of this KT motif in solution in the case of SAM-I riboswitch RNA. , With a variety of structure-probing experiments, the above two experimental results suggested that the bimodal stability of the kink-turn motif is important for the riboswitch function.…”

Temperature Induced Dynamical Transition of Biomolecules in Polarizable and Nonpolarizable TIP3P Water

“…Hydration affects the dynamics of RNA significantly more than those of a globular protein (lysozyme). In fact, as reported, the structural differences between RNA and protein result in slower dynamics, motional heterogeneity, and heterogeneous hydration on the molecular surface of RNA . Yet, the DT of RNA (like protein) is initiated by sudden change of hydration water mobility at its FSC temperature .…”

“…Subsequently while heating, bimolecular motions as often measured by atomistic mean-square displacement (MSD) increase linearly with temperature up to certain onset temperature, at which suddenly they exhibit a sharp transition to a nonlinear temperature dependence. In parallel with the glass transition temperature in a glassy substance, the onset temperature of anharmonicity in a biomolecular system − is referred to as the dynamical transition (DT) − temperature, T DT .…”

Molecular Dynamics and NMR Shed Light on Motions Underpinning Dynamical Transitions in Biomolecules

“…The detailed analysis of the simulated MD trajectories presented by Frank et al (10) includes extraction of global motions through principal component analysis, as well as specifics of the motions of individual bond vectors. The analysis shows that even in this system, designed to be simple to interpret, there is motional heterogeneity along the molecule in addition to the approximately threedimensional hinge-bending motion of the two helical segments.…”