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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

The tasks of designing RNAs are discrete optimization problems, and several versions of these problems are NP-hard. As an alternative to commonly used local search methods, we formulate these problems as continuous optimization and develop…

Biomolecules · Quantitative Biology 2024-03-04 Ning Dai , Wei Yu Tang , Tianshuo Zhou , David H. Mathews , Liang Huang

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…

Designing therapeutic messenger RNA (mRNA) requires creating full-length transcripts that carefully balance stability, translation efficiency, and immune safety. To address this challenge, we propose ProMORNA, a multi-objective generation…

Machine Learning · Computer Science 2026-05-05 Zixi Shao , Tao Wang , Yibei Xiao , Tianyi Huang

The design of multi-stable RNA molecules has important applications in biology, medicine, and biotechnology. Synthetic design approaches profit strongly from effective in-silico methods, which can tremendously impact their cost and…

Quantitative Methods · Quantitative Biology 2018-06-24 Stefan Hammer , Yann Ponty , Wei Wang , Sebastian Will

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

Protein design using structure prediction models such as AlphaFold2 has shown remarkable success, but existing approaches like relaxed sequence optimization (RSO) rely on single-path gradient descent and ignore sequence-space constraints,…

Machine Learning · Computer Science 2025-10-29 Joohwan Ko , Aristofanis Rontogiannis , Yih-En Andrew Ban , Axel Elaldi , Nicholas Franklin

Messenger RNA (mRNA) vaccines and therapeutics are emerging as powerful tools against a variety of diseases, including infectious diseases and cancer. The design of mRNA molecules, particularly the untranslated region (UTR) and coding…

Biomolecules · Quantitative Biology 2024-10-29 Yang Liu , Jie Gao , Xiaonan Zhang , Xiaomin Fang

Protein sequence design methods have demonstrated strong performance in sequence generation for de novo protein design. However, as the training objective was sequence recovery, it does not guarantee designability--the likelihood that a…

Machine Learning · Computer Science 2025-06-03 Fanglei Xue , Andrew Kubaney , Zhichun Guo , Joseph K. Min , Ge Liu , Yi Yang , David Baker

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

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

RNA design, the task of finding a sequence that folds into a target secondary structure, has broad biological and biomedical impact but remains computationally challenging due to the exponentially large sequence space and exponentially many…

Machine Learning · Computer Science 2026-02-16 Milan Gautam , Ning Dai , Tianshuo Zhou , Bowen Xie , David Mathews , Liang Huang

Sampling one or more effective solutions from large search spaces is a recurring idea in machine learning, and sequential optimization has become a popular solution. Typical examples include data summarization, sample mining for predictive…

Sampling-based algorithms are widely used for motion planning in high-dimensional configuration spaces. However, due to low sampling efficiency, their performance often diminishes in complex configuration spaces with narrow corridors.…

Robotics · Computer Science 2025-07-22 Lu Huang , Lingxiao Meng , Jiankun Wang , Xingjian Jing

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with…

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

Rising costs in recent years of developing new drugs and treatments have led to extensive research in optimization techniques in biomolecular design. Currently, the most widely used approach in biomolecular design is directed evolution,…

Machine Learning · Computer Science 2021-11-09 Alexander Whatley , Zhekun Luo , Xiangru Tang

Space filling designs are central to studying complex systems in various areas of science. They are used for obtaining an overall understanding of the behaviour of the response over the input space, model construction and uncertainty…

Methodology · Statistics 2016-08-10 Shirin Golchi , Jason L. Loeppky

While RNA technologies hold immense therapeutic potential in a range of applications from vaccination to gene editing, the broad implementation of these technologies is hindered by the challenge of delivering these agents effectively. Lipid…

Biomolecules · Quantitative Biology 2023-08-30 Daisy Yi Ding , Yuhui Zhang , Yuan Jia , Jiuzhi Sun

A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that…

Machine Learning · Computer Science 2023-04-10 Patrick Emami , Aidan Perreault , Jeffrey Law , David Biagioni , Peter C. St. John
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