RNAiFold 2.0: A web server and software to design custom and Rfam-based RNA molecules

TL;DR

RNAiFold 2.0 is an advanced software tool that uses constraint programming for exhaustive RNA inverse folding, enabling the design of synthetic RNA molecules with specific structures and functions, including Rfam-based constructs and hybrid complexes.

Contribution

It introduces a comprehensive C++ implementation of RNAiFold 2.0 with new features like amino acid constraints and expanded structure compatibility, enhancing RNA design capabilities.

Findings

Supports design of Rfam-based RNA constructs

Allows hybridization complex design of two RNA molecules

Provides exhaustive solution generation for target structures

Abstract

Several algorithms for RNA inverse folding have been used to design synthetic riboswitches, ribozymes and thermoswitches, whose activity has been experimentally validated. The RNAiFold software is unique among approaches for inverse folding in that (exhaustive) constraint programming is used instead of heuristic methods. For that reason, RNAiFold can generate all sequences that fold into the target structure, or determine that there is no solution. RNAiFold 2.0 is a complete overhaul of RNAiFold 1.0, rewritten from the now defunct COMET language to C++. The new code properly extends the capabilities of its predecessor by providing a user-friendly pipeline to design synthetic constructs having the functionality of given Rfam families. In addition, the new software supports amino acid constraints, even for proteins translated in different reading frames from overlapping coding sequences; moreover, structure compatibility/incompatibility constraints have been expanded. With these features, RNAiFold 2.0 allows the user to design single RNA molecules as well as hybridization complexes of two RNA molecules. The web server, source code and linux binaries are publicly accessible at http://bioinformatics.bc.edu/clotelab/RNAiFold2.0