The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Differentiable Partition Function Calculation for RNA
Open accessPreprint — published as 10.1093/nar/gkad1168
Abstract
A bstract: Ribonucleic acid (RNA) is an essential molecule in a wide range of biological functions. In 1990, McCaskill introduced a dynamic programming algorithm for computing the partition function of an RNA sequence. This forward model is widely used for understanding the thermodynamic properties of a given RNA. In this work, we introduce a generalization of McCaskill’s algorithm that is well-defined over continuous inputs and is differentiable. This allows us to tackle the inverse folding problem—designing a sequence with desired equilibrium thermodynamic properties—directly using gradient optimization. This has applications to creating RNA-based drugs such as mRNA vaccines. Furthermore, it allows McCaskill’s foundational algorithm to be incorporated into machine learning pipelines directly since we have made it end-to-end differentiable. This work highlights how principles from differentiable programming can be translated to existing physical models to develop powerful tools for machine learning. We provide a concrete example by implementing an effective and interpretable RNA design algorithm.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Matthies, M., Krueger, R., Torda, A., & Ward, M.
- Affiliations
- Universität Hamburg (DE)
- Harvard University (US)
- The University of Western Australia (AU)
- Corresponding author
- Ward, Max
- Venue
- Nucleic Acids Research
- Publisher
- openRxiv
- Published
- 2023-01-31
- Volume
- 52
- Issue
- 3
- Pages
- e14-e14
- ISSN
- 0305-1048 (ISSN-L)
- PMC
- PMC10853804
- OpenAlex
- W4389243865
- Cited by
- 15
- References
- 1
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Harvard University
- Universität Hamburg
- Office of Naval Research (N00014-17- 1-3029, N00014-17-1, N00014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Mathematics › Theoretical Computer Science › DNA and Biological Computing
- Keywords
- differentiable programming, RNA thermodynamics, RNA folding, continuous dynamic programming
- MeSH terms
- Algorithms, Nucleic Acid Conformation, RNA, Thermodynamics
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