ArticleNature communications2025
Designing molecular RNA switches with Restricted Boltzmann machines.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Rational design of mechanically active RNAs: de novo engineering of functional exoribonuclease-resistant RNAs.Nucleic acids research · 2026Article
- RNA design: update on computational frameworks and programs for inverse RNA folding.Briefings in bioinformatics · 2026Review
- Integrating experimental feedback improves generative models for biological sequences.Nucleic acids research · 2025Article
- Deterministic Versus Nondeterministic Optimization Algorithms for the Restricted Boltzmann Machine.Journal of computational and cognitive engineering · 2024Article
- Towards parsimonious generative modeling of RNA families.Nucleic acids research · 2024Article
- Applications of artificial intelligence and machine learning in dynamic pathway engineering.Biochemical Society transactions · 2023Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Riboswitches are structured allosteric RNA molecules that change conformation upon metabolite binding, triggering a regulatory response. Here we focus on the de novo design of riboswitch-like aptamers, the core part of the riboswitch undergoing structural changes. We use Restricted Boltzmann machines (RBM) to learn generative models from homologous sequence data. We first verify, on four different riboswitch families, that RBM-generated sequences correctly capture the conservation, covariation and diversity of natural aptamers. The RBM model is then used to design new SAM-I riboswitch aptamers. To experimentally validate the properties of the structural switch in designed molecules, we resort to chemical probing (SHAPE and DMS), and develop a tailored analysis pipeline adequate for high-throughput tests of diverse sequences. We probe a total of 476 RBM-designed and 201 natural sequences. Designed molecules with high RBM scores, with 20% to 40% divergence from any natural sequence, display ≈ 30% success rate of responding to SAM with a structural switch similar to their natural counterparts. We show how the capability of the designed molecules to switch conformation is connected to fine energetic features of their structural components.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.