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Optimizing the mRNA codon has an essential impact on gene expression for a specific target protein. It is an NP-hard problem; thus, exact solutions to such optimization problems become computationally intractable for realistic problem sizes…

Quantum Physics · Physics 2024-05-13 Hongfeng Zhang , Aritra Sarkar , Koen Bertels

mRNA technology has revolutionized vaccine development, protein replacement therapies, and cancer immunotherapies, offering rapid production and precise control over sequence and efficacy. However, the inherent instability of mRNA poses…

Biomolecules · Quantitative Biology 2025-03-26 Max Ward , Mary Richardson , Mihir Metkar

Accurate prediction of mRNA secondary structure is critical for understanding gene expression, translation efficiency, and advancing mRNA-based therapeutics. However, the combinatorial complexity of possible foldings, especially in long…

Recent advancements in quantum computing have opened new avenues for tackling long-standing complex combinatorial optimization problems that are intractable for classical computers. Predicting secondary structure of mRNA is one such…

Messenger RNA (mRNA) vaccines are being used for COVID-19, but still suffer from the critical issue of mRNA instability and degradation, which is a major obstacle in the storage, distribution, and efficacy of the vaccine. Previous work…

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

Messenger RNA (mRNA) sequences as therapeutics require optimized design to ensure efficient translation, structural stability, and minimal immunogenicity. This study presents a two-stage in-silico framework that integrates deep learning and…

Computation and Language · Computer Science 2026-05-28 Dhawa Sang Dong , Mausam Gurung , Suraj Kandel

Advances in de novo synthesis of DNA and computational gene design methods make possible the customization of genes by direct manipulation of features such as codon bias and mRNA secondary structure. Codon context is another feature…

Data Structures and Algorithms · Computer Science 2015-08-17 Dimitris Papamichail , Hongmei Liu , Vitor Machado , Nathan Gould , J. Robert Coleman , Georgios Papamichail

It is the first step for understanding how RNA structure folds from base sequences that to know how its secondary structure is formed. Traditional energy-based algorithms are short of precision, particularly for non-nested sequences, while…

Quantum Physics · Physics 2023-05-18 Ji Jiang , Qipeng Yan , Ye Li , Min Lu , Ziwei Cui , Menghan Dou , Qingchun Wang , Yu-Chun Wu , Guo-Ping Guo

The mRNA optimization is critical for therapeutic and biotechnological applications, since sequence features directly govern protein expression levels and efficacy. However, current methods face significant challenges in simultaneously…

Quantitative Methods · Quantitative Biology 2025-06-02 Zheng Gong , Ziyi Jiang , Weihao Gao , Deng Zhuo , Lan Ma

Generating protein sequences conditioned on protein structures is an impactful technique for protein engineering. When synthesizing engineered proteins, they are commonly translated into DNA and expressed in an organism such as yeast. One…

Machine Learning · Computer Science 2024-09-27 Hannes Stark , Umesh Padia , Julia Balla , Cameron Diao , George Church

Background: The secondary structure and complexity of mRNA influences its accessibility to regulatory molecules (proteins, micro-RNAs), its stability and its level of expression. The mobile elements of the RNA sequence, the wobble bases,…

Biomolecules · Quantitative Biology 2008-07-22 Jan C. Biro

Computational methods are the most effective tools we have besides scientific experiments to explore the properties of complex biological systems. Progress is slowing because digital silicon computers have reached their limits in terms of…

Quantum Physics · Physics 2020-04-03 Viv Kendon

We describe a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots. The algorithm has a worst case complexity of ${\cal O}(N^6)$ in time and ${\cal O}(N^4)$ in storage. The description of the…

Biological Physics · Physics 2009-09-25 Elena Rivas , Sean R. Eddy

Predicting the secondary structure of RNA is a core challenge in computational biology, essential for understanding molecular function and designing novel therapeutics. The field has evolved from foundational but accuracy-limited…

Biomolecules · Quantitative Biology 2026-05-20 Giuseppe Sacco , Giovanni Bussi , Guido Sanguinetti

Optimizing the properties of molecules (materials or drugs) for stronger toughness, lower toxicity, or better bioavailability has been a long-standing challenge. In this context, we propose a molecular optimization framework called Q-Drug…

Quantum Physics · Physics 2023-08-28 Zhaoping Xiong , Xiaopeng Cui , Xinyuan Lin , Feixiao Ren , Bowen Liu , Yunting Li , Manhong Yung , Nan Qiao

Due to the hierarchical organization of RNA structures and their pivotal roles in fulfilling RNA functions, the formation of RNA secondary structure critically influences many biological processes and has thus been a crucial research topic.…

RNAs self-interact through hydrogen-bond base-pairing between nucleotides and fold into specific, stable structures that substantially govern their biochemical behaviour. Experimental characterization of these structures remains difficult,…

Quantum Physics · Physics 2023-05-02 Tristan Zaborniak , Juan Giraldo , Hausi Müller , Hosna Jabbari , Ulrike Stege

As we rapidly approach the frontiers of ultra large computing resources, software optimization is becoming of paramount interest to scientific application developers interested in efficiently leveraging all available on-Node computing…

Computational prediction of RNA structures is an important problem in computational structural biology. Studies of RNA structure formation often assume that the process starts from a fully synthesized sequence. Experimental evidence,…

Biomolecules · Quantitative Biology 2021-04-28 Vo Hong Thanh , Dani Korpela , Pekka Orponen
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