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RNA inverse folding, designing sequences to form specific 3D structures, is critical for therapeutics, gene regulation, and synthetic biology. Current methods, focused on sequence recovery, struggle to address structural objectives like…

Machine Learning · Computer Science 2026-01-28 Qi Si , Xuyang Liu , Penglei Wang , Xin Guo , Yuan Qi , Yuan Cheng

RNA's diverse biological functions stem from its structural versatility, yet accurately predicting and designing RNA sequences given a 3D conformation (inverse folding) remains a challenge. Here, I introduce a deep learning framework that…

Quantitative Methods · Quantitative Biology 2026-01-06 Annabelle Yao

The rapid development of the DNA nanotechnology field has been facilitated by advances in CAD software. However, as more complex concepts arose, the lag between the needs and software capabilities appeared. Further derailed by manual…

Quantitative Methods · Quantitative Biology 2021-11-30 Samson Petrosyan , Grigory Tikhomirov

RNA design aims to find a sequence that folds with highest probability into a designated target structure. However, certain structures are undesignable, meaning no sequence can fold into the target structure under the default (Turner) RNA…

Data Structures and Algorithms · Computer Science 2025-05-06 Tianshuo Zhou , Wei Yu Tang , Apoorv Malik , David H. Mathews , Liang Huang

Atomically detailed simulations of RNA folding have proven very challenging in view of the difficulties of developing realistic force fields and the intrinsic computational complexity of sampling rare conformational transitions. To tackle…

Soft Condensed Matter · Physics 2022-05-26 Gianmarco Lazzeri , Cristian Micheletti , Samuela Pasquali , Pietro Faccioli

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

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

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

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

The RNA inverse folding problem, a key challenge in RNA design, involves identifying nucleotide sequences that can fold into desired secondary structures, which are critical for ensuring molecular stability and function. The inherent…

Computer Vision and Pattern Recognition · Computer Science 2025-12-04 Guang Yang , Lei Fan

Protein inverse folding, the design of an amino acid sequence based on a target protein structure, is a fundamental problem of computational protein engineering. Existing methods either generate sequences without leveraging external…

Quantitative Methods · Quantitative Biology 2026-03-10 Jin Han , Tianfan Fu , Wu-Jun Li

Predicting the consensus structure of a set of aligned RNA homologs is a convenient method to find conserved structures in an RNA genome, which has many applications including viral diagnostics and therapeutics. However, the most commonly…

Biomolecules · Quantitative Biology 2024-07-08 Apoorv Malik , Liang Zhang , Milan Gautam , Ning Dai , Sizhen Li , He Zhang , David H. Mathews , Liang Huang

How can we design protein sequences folding into the desired structures effectively and efficiently? AI methods for structure-based protein design have attracted increasing attention in recent years; however, few methods can simultaneously…

Artificial Intelligence · Computer Science 2023-04-14 Zhangyang Gao , Cheng Tan , Pablo Chacón , Stan Z. Li

The field of RNA secondary structure prediction has made significant progress with the adoption of deep learning techniques. In this work, we present the RNAformer, a lean deep learning model using axial attention and recycling in the…

Machine Learning · Computer Science 2023-07-20 Jörg K. H. Franke , Frederic Runge , Frank Hutter

The Nearest Neighbor model is the $\textit{de facto}$ thermodynamic model of RNA secondary structure formation and is a cornerstone of RNA structure prediction and sequence design. The current functional form (Turner 2004) contains…

Biomolecules · Quantitative Biology 2025-05-13 Ryan K. Krueger , Sharon Aviran , David H. Mathews , Jeffrey Zuber , Max Ward

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

We consider the inverse-folding problem for RNA secondary structures: for a given (pseudo-knot-free) secondary structure find a sequence that has that structure as its ground state. If such a sequence exists, the structure is called…

Biological Physics · Physics 2015-06-26 Bernd Burghardt , Alexander K. Hartmann

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray…

Biomolecules · Quantitative Biology 2015-06-11 Tristan Cragnolini , Philippe Derreumaux , Samuela Pasquali

Molecule inverse folding has been a long-standing challenge in chemistry and biology, with the potential to revolutionize drug discovery and material science. Despite specified models have been proposed for different small- or…

Artificial Intelligence · Computer Science 2024-05-30 Zhangyang Gao , Jue Wang , Cheng Tan , Lirong Wu , Yufei Huang , Siyuan Li , Zhirui Ye , Stan Z. Li

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…