Ab initio RNA folding

TL;DR

This review discusses recent advances in physics-based computational models for RNA 3D structure prediction, highlighting their ability to predict equilibrium, dynamical, and thermodynamical properties, and addressing current challenges.

Contribution

It provides a comprehensive overview of physics-based RNA folding models, emphasizing recent developments and their advantages over bioinformatics approaches.

Findings

Physics-based models predict equilibrium structures effectively.

Models can explore RNA folding dynamics and thermodynamics.

Open challenges include incorporating more key interactions.

Abstract

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.