Elastic network models capture the motions apparent within ensembles of RNA structures

Abstract

The role of structure and dynamics in mechanisms for RNA becomes increasingly important. Computational approaches using simple dynamics models have been successful at predicting the motions of proteins and are often applied to ribonucleoprotein complexes but have not been thoroughly tested for well-packed nucleic acid structures. In order to characterize a true set of motions, we investigate the apparent motions from 16 ensembles of experimentally determined RNA structures. These indicate a relatively limited set of motions that are captured by a small set of principal components (PCs). These limited motions closely resemble the motions computed from low frequency normal modes from elastic network models (ENMs), either at atomic or coarse-grained resolution. Various ENM model types, parameters, and structure representations are tested here against the experimental RNA structural ensembles, exposing differences between models for proteins and for folded RNAs. Differences in performance are seen, depending on the structure alignment algorithm used to generate PCs, modulating the apparent utility of ENMs but not significantly impacting their ability to generate functional motions. The loss of dynamical information upon coarse-graining is somewhat larger for RNAs than for globular proteins, indicating, perhaps, the lower cooperativity of the less densely packed RNA. However, the RNA structures show less sensitivity to the elastic network model parameters than do proteins. These findings further demonstrate the utility of ENMs and the appropriateness of their application to well-packed RNA-only structures, justifying their use for studying the dynamics of ribonucleo-proteins, such as the ribosome and regulatory RNAs.

Ribosome Mechanics Informs about Mechanism

“…We [66] showed that the motions apparent from multiple tRNA structures closely resemble those observed in the elastic network simulations. The first three most important normal mode motions of the tRNA are shown in Fig.…”

Elastic network models for RNA: a comparative assessment with molecular dynamics and SHAPE experiments

“…For the comparative validation against MD and SHAPE data we consider eight different types of elastic networks, as summarized in Table II. A subset of the considered models have been previously used in different contexts [23,[32][33][34]. With the exception of the allatom (AA) model, all other ENMs will be referred to with the one, two and three-letter acronyms corresponding to which of the phosphate (P), sugar (S), or base (B) interaction centers are used, see Fig.…”

“…The development and performance assessment of elastic networks for RNAs have so far been pursued in two main directions. On one hand, Zimmermann and Jernigan [32] have recently shown that the essential dynamical spaces of ENMs based on the phosphate representation of RNAs can satisfactorily account for the structural variability observed across crystal structures homologs. On the other hand, Setny and Zacharias [33] have considered ENMs where different atoms of the RNA backbone (i.e.…”

“…More recently, Setny and Zacharias suggested that the best candidate to host a single ENM bead is the center of the ribose sugar in the backbone [33]. Other ENMs with more beads per nucleotide have also been used [23,27,32,34]. Most of these studies assessed the validity of different representations by focusing on their capability to reproduce either the structural variability observed across experimental conformers or the Debye-Waller factors from X-ray experiments.…”

Barnaba: Software for Analysis of Nucleic Acids Structures and Trajectories

“…They assume that the system can be represented as a set of beads connected by harmonic springs, each having rest length equal to the distance between the two beads it connects, in a reference structure (usually, an experimental structure from the PDB). First introduced to analyze protein dynamics Tirion ( 1996 ), ENMs are also applicable to structured RNA molecules Bahar and Jernigan ( 1998 ); Setny and Zacharias ( 2013 ); Zimmermann and Jernigan ( 2014 ). Barnaba contains routines to construct ENM of nucleic acids and proteins, and, as unique feature, makes it possible to calculate 2uctuations between consecutive C2-C2 atoms.…”