Energy-directed RNA structure prediction

Abstract

In this chapter we present the classic dynamic programming algorithms for RNA structure prediction by energy minimization, as well as variations of this approach that allow to compute suboptimal foldings, or even the partition function over all possible secondary structures. The latter are essential in order to deal with the inaccuracy of minimum free energy (MFE) structure prediction, and can be used, for example, to derive reliability measures that assign a confidence value to all or part of a predicted structure. In addition, we discuss recently proposed alternatives to the MFE criterion such as the use of maximum expected accuracy (MEA) or centroid structures. The dynamic programming algorithms implicitly assume that the RNA molecule is in thermodynamic equilibrium. However, especially for long RNAs, this need not be the case. In the last section we therefore discuss approaches for predicting RNA folding kinetics and co-transcriptional folding.