Predicting RNA 3D structure using a coarse-grain helix-centered model.

Peter Kerpedjiev,Ivo L Hofacker,Christian Höner Zu Siederdissen

doi:10.1261/rna.047522.114

Peter Kerpedjiev, Ivo L Hofacker + Show 1 more

Open Access

https://doi.org/10.1261/rna.047522.114

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Abstract

A 3D model of RNA structure can provide information about its function and regulation that is not possible with just the sequence or secondary structure. Current models suffer from low accuracy and long running times and either neglect or presume knowledge of the long-range interactions which stabilize the tertiary structure. Our coarse-grained, helix-based, tertiary structure model operates with only a few degrees of freedom compared with all-atom models while preserving the ability to sample tertiary structures given a secondary structure. It strikes a balance between the precision of an all-atom tertiary structure model and the simplicity and effectiveness of a secondary structure representation. It provides a simplified tool for exploring global arrangements of helices and loops within RNA structures. We provide an example of a novel energy function relying only on the positions of stems and loops. We show that coupling our model to this energy function produces predictions as good as or better than the current state of the art tools. We propose that given the wide range of conformational space that needs to be explored, a coarse-grain approach can explore more conformations in less iterations than an all-atom model coupled to a fine-grain energy function. Finally, we emphasize the overarching theme of providing an ensemble of predicted structures, something which our tool excels at, rather than providing a handful of the lowest energy structures.

Highlights

Structured noncoding RNAs are an integral part of every cell
We propose an approach that bridges the gap between abstract secondary structure prediction and concrete all-atomic prediction with a coarse-grained tertiary structure prediction and sampling approach for RNAs
We have presented a coarse-grained model of RNA structure parameterized by the angles and shifts between helices

Summary

Introduction

In contrast to mRNAs, whose main duty is being the messenger in the construction of proteins from DNA genes, noncoding RNAs are involved in many regulatory and functional processes In these roles, the three-dimensional structure of an ncRNA is of more importance than the sequence of nucleotides making up the molecule. The structure, is largely determined by the self-folding of the sequence This structural importance has led to many approaches to predict either the two-dimensional secondary structure (Zuker 2003; Do et al 2006; Lorenz et al 2011) or the three-dimensional tertiary structure (Das and Baker 2007; Ding et al 2008; Parisien and Major 2008; Frellsen et al 2009; Jonikas et al 2009; Popenda et al 2012; Zhao et al 2012). These downsides are, balanced by the additional information encoded in the tertiary structure

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