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The task of RNA design given a target structure aims to find a sequence that can fold into that structure. It is a computationally hard problem where some version(s) have been proven to be NP-hard. As a result, heuristic methods such as…

Biomolecules · Quantitative Biology 2024-12-13 Wei Yu Tang , Ning Dai , Tianshuo Zhou , David H. Mathews , Liang Huang

RNA design aims to identify RNA sequences that fold into a target secondary structure. This task is challenging in terms of computational efficiency. Most existing methods focus on either minimum free energy (MFE)-based or ensemble-based…

Biomolecules · Quantitative Biology 2026-03-04 Tianshuo Zhou , David H. Mathews , Liang Huang

Motivation: RNA design aims to find RNA sequences that fold into a given target secondary structure, a problem also known as RNA inverse folding. However, not all target structures are designable. Recent advances in RNA designability have…

Data Structures and Algorithms · Computer Science 2026-04-28 Tianshuo Zhou , David H. Mathews , Liang Huang

Designing messenger RNA (mRNA) sequences for a fixed target protein requires searching an exponentially large synonymous space while optimizing properties that affect stability and downstream performance. This is challenging because…

Biomolecules · Quantitative Biology 2026-03-09 Feipeng Yue , Ning Dai , Wei Yu Tang , Tianshuo Zhou , David H. Mathews , Liang Huang

The problem of RNA secondary structure design (also called inverse folding) is the following: given a target secondary structure, one aims to create a sequence that folds into, or is compatible with, a given structure. In several practical…

Quantitative Methods · Quantitative Biology 2013-08-02 Yu Zhou , Yann Ponty , Stéphane Vialette , Jérôme Waldispühl , Yi Zhang , Alain Denise

When modeling an application of practical relevance as an instance of a combinatorial problem X, we are often interested not merely in finding one optimal solution for that instance, but in finding a sufficiently diverse collection of good…

Data Structures and Algorithms · Computer Science 2026-02-19 Julien Baste , Michael R. Fellows , Lars Jaffke , Tomáš Masařík , Mateus de Oliveira Oliveira , Geevarghese Philip , Frances A. Rosamond

Nucleic acid sequence design via codon optimization is a fundamental task with applications across synthetic biology, mRNA therapeutics, and vaccine design. Given a target protein, it is a major open challenge to navigate the…

Quantitative Methods · Quantitative Biology 2026-04-22 Mark Fornace , Christina Wuyan Wang , Michael Lindsey

Background: Designing amino acid sequences that are stable in a given target structure amounts to maximizing a conditional probability. A straightforward approach to accomplish this is a nested Monte Carlo where the conformation space is…

Soft Condensed Matter · Physics 2016-08-31 Anders Irbäck , Carsten Peterson , Frank Potthast , Erik Sandelin

RNA co-transcriptionality, where RNA is spliced or folded during transcription from DNA templates, offers promising potential for molecular programming. It enables programmable folding of nano-scale RNA structures and has recently been…

Formal Languages and Automata Theory · Computer Science 2025-07-01 Da-Jung Cho , Szilárd Zsolt Fazekas , Shinnosuke Seki , Max Wiedenhöft

Designing RNA molecules has garnered recent interest in medicine, synthetic biology, biotechnology and bioinformatics since many functional RNA molecules were shown to be involved in regulatory processes for transcription, epigenetics and…

Machine Learning · Computer Science 2019-04-15 Frederic Runge , Danny Stoll , Stefan Falkner , Frank Hutter

Artificial RNA molecules with novel functionality have many applications in synthetic biology, pharmacy and white biotechnology. The de novo design of such devices using computational methods and prediction tools is a resource-efficient…

Biomolecules · Quantitative Biology 2019-05-13 Stefan Hammer , Christian Günzel , Mario Mörl , Sven Findeiß

In this paper we present a sampling framework for RNA structures of fixed topological genus. We introduce a novel, linear time, uniform sampling algorithm for RNA structures of fixed topological genus $g$, for arbitrary $g>0$. Furthermore…

Computational Engineering, Finance, and Science · Computer Science 2013-04-30 Fenix W. D. Huang , Markus E. Nebel , Christian M. Reidys

High-quality training datasets are crucial for the development of effective protein design models, but existing synthetic datasets often include unfavorable sequence-structure pairs, impairing generative model performance. We leverage…

Fragment-based shape signature techniques have proven to be powerful tools for computer-aided drug design. They allow scientists to search for target molecules with some similarity to a known active compound. They do not require reference…

Artificial Intelligence · Computer Science 2022-01-05 Thierry Petit , Randy J. Zauhar

RNA inverse sequence design has broad biological and engineering applications, but computational methods for practical design queries remain limited. Such queries may impose several constraints at once, including target folds or motifs,…

Quantitative Methods · Quantitative Biology 2026-05-11 Michael Lindsey

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete…

Quantitative Methods · Quantitative Biology 2015-06-22 Jozef Haleš , Ján Maňuch , Yann Ponty , Ladislav Stacho

In this paper, we present fixed-parameter tractability algorithms for both the undirected and directed versions of the Spanning Tree Isomorphism Problem, parameterized by the size $k$ of a redundant set. A redundant set is a collection of…

Data Structures and Algorithms · Computer Science 2025-08-08 Fangjian Shen , Yicheng Zheng , Wushao Wen , Hankz Hankui Zhuo

Background. Dramatic increases in RNA structural data have made it possible to recognize its conformational preferences much better than a decade ago. This has created an opportunity to use discrete restraint-based conformational sampling…

Biomolecules · Quantitative Biology 2007-10-23 Swanand Gore , Tom Blundell

Probabilistic representations, such as Bayesian and Markov networks, are fundamental to much of statistical machine learning. Thus, learning probabilistic representations directly from data is a deep challenge, the main computational…

Machine Learning · Computer Science 2018-09-20 Andreas Bueff , Stefanie Speichert , Vaishak Belle

Solving the RNA inverse folding problem is a critical prerequisite to RNA design, an emerging field in bioengineering with a broad range of applications from reaction catalysis to cancer therapy. Although significant progress has been made…

Quantitative Methods · Quantitative Biology 2019-03-07 Jade Shi , Rhiju Das , Vijay S. Pande
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