MultiRNAFold

MultiRNAFold predicts pseudoknot-free minimum free energy secondary structures for single and multiple interacting RNA and DNA molecules to analyze nucleic acid interactions and support design of ribozymes, oligonucleotides, and nucleic acid nanostructures.

Key Features:

• Integrated components: SimFold, PairFold, and MultiFold are integrated to enable analysis of one or multiple interacting nucleic acids.
• Secondary Structure Prediction: Predicts minimum free energy pseudoknot-free secondary structures for RNA and DNA sequences and their interactions.
• Alternative Low-Energy Structures: Predicts alternative sub-optimal low-energy secondary structures by evaluating 100 sub-optimal foldings, with the best sub-optimal folding reported (average accuracy 91% versus 79% for MFE in reported tests).
• Algorithmic Foundations: Extends the Zuker and Stiegler free energy minimization algorithm and incorporates elements of Wuchty et al.'s sub-optimal folding approach.
• Performance Analysis: Validated against known interacting RNA secondary structures from the literature using tests on 17 sequences up to 200 nucleotides that do not form pseudoknots, with accuracy decreasing for longer sequences and increased pseudoknot/tertiary complexity.

Scientific Applications:

• Ribozyme design: Supports structural design and analysis of ribozymes by predicting secondary structures and alternative foldings.
• Oligonucleotide design: Informs primer-target affinity and antisense oligonucleotide design by modeling interacting nucleic acid secondary structures.
• DNA code word design: Assists design of DNA code words through prediction of secondary structure constraints.
• Nucleic acid nanostructures: Aids design and analysis of nucleic acid nanostructures by providing predicted secondary and alternative low-energy structures for interacting strands.

Methodology:

Computational free energy minimization using an extension of the Zuker and Stiegler algorithm, incorporation of Wuchty et al.'s sub-optimal folding approach, evaluation of 100 sub-optimal foldings, and pseudoknot-free multi-molecule interaction modeling.