Simulation of Folding Kinetics for Aligned RNAs.

Jiabin Huang,Björn Voß

doi:10.3390/genes12030347

Abstract

Studying the folding kinetics of an RNA can provide insight into its function and is thus a valuable method for RNA analyses. Computational approaches to the simulation of folding kinetics suffer from the exponentially large folding space that needs to be evaluated. Here, we present a new approach that combines structure abstraction with evolutionary conservation to restrict the analysis to common parts of folding spaces of related RNAs. The resulting algorithm can recapitulate the folding kinetics known for single RNAs and is able to analyse even long RNAs in reasonable time. Our program RNAliHiKinetics is the first algorithm for the simulation of consensus folding kinetics and addresses a long-standing problem in a new and unique way.

Highlights

The structure–function relationship is a generally accepted and often documented property of RNAs, be it non-coding, messenger, ribosomal, transfer or other RNAs
We needed to develop an algorithm for the prediction of hishapes for a set of aligned sequences and adopt the free energy evaluation of the folding pathway heuristics to work on alignments
It offers support for alignments as input, so that we only had to design an algebra for the combined free energy and covariation scoring

Summary

Introduction

The structure–function relationship is a generally accepted and often documented property of RNAs, be it non-coding, messenger, ribosomal, transfer or other RNAs. Structure formation is driven by thermodynamics with the goal to minimise free energy, but it is not guaranteed that thermodynamic equilibrium is reached. Structure formation is driven by thermodynamics with the goal to minimise free energy, but it is not guaranteed that thermodynamic equilibrium is reached This is not a problem because evolution selects by function and not by structure, but computationally this means that the biologically active structure is not the one we can predict by free energy minimisation. The structure needs to fold back into the initial conformation upon ligand release to ensure correct function. These functionalities are encoded in the folding kinetics of the respective

Methods

Results

Conclusion