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PreprintCC BY-NC-NDbioRxiv

fuzzyfold: a high-performance framework for stochastic RNA folding kinetics

  1. 1University of Vienna

Abstract

The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.

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BibTeX
@misc{badelt2026fuzzyfold,
  title = {{fuzzyfold: a high-performance framework for stochastic RNA folding kinetics}},
  author = {S. Badelt},
  howpublished = {bioRxiv},
  year = {2026},
  month = jun,
  doi = {10.64898/2026.06.17.732885},
  url = {https://www.biorxiv.org/content/10.64898/2026.06.17.732885v2},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - fuzzyfold: a high-performance framework for stochastic RNA folding kinetics
AU  - S. Badelt
PY  - 2026
DA  - 2026/06/17
PB  - bioRxiv
DO  - 10.64898/2026.06.17.732885
UR  - https://www.biorxiv.org/content/10.64898/2026.06.17.732885v2
AB  - The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.
ER  -