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Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
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The trRosettaRNA server for RNA structure prediction.

Wenkai Wang1, Xiaocheng Liu1, Zhenling Peng1

  • 1MOE Frontiers Science Center for Nonlinear Expectations, State Key Laboratory of Cryptography and Digital Economy Security, Shandong Province Key Laboratory of Financial Risk, Research Center for Mathematics and Interdisciplinary Sciences, Shandong University, Qingdao, China.

Nature Protocols
|April 8, 2026
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Summary
This summary is machine-generated.

trRosettaRNA is a deep learning-based server for automated RNA 3D structure prediction. It offers high accuracy and flexibility, aiding research in understanding RNA functions and structures.

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Area of Science:

  • Computational Biology
  • Structural Biology
  • Bioinformatics

Background:

  • RNA molecules fold into complex three-dimensional (3D) structures essential for their biological functions, analogous to proteins.
  • Accurate prediction of these RNA 3D structures is crucial for understanding their roles in cellular processes.

Purpose of the Study:

  • To introduce trRosettaRNA, a novel web-based platform for automated RNA 3D structure prediction utilizing deep learning.
  • To provide researchers with a tool for accurate and efficient prediction of RNA tertiary structures.

Main Methods:

  • Development of an end-to-end deep learning neural network for direct RNA 3D structure prediction from nucleotide sequences.
  • Integration of optional inputs for custom multiple sequence alignments and secondary structures to enhance prediction accuracy.
  • Inclusion of an energy optimization step to refine predicted structures and resolve potential violations.

Main Results:

  • The trRosettaRNA server demonstrates state-of-the-art modeling accuracy for RNA 3D structure prediction.
  • Predictions for RNA families lacking known 3D structures showed high confidence and good agreement with experimental data.
  • Median prediction time for a 200-nucleotide RNA sequence is approximately 1 hour using 5 CPU cores.

Conclusions:

  • trRosettaRNA offers a powerful, accurate, and user-friendly solution for automated RNA 3D structure prediction.
  • The availability of both a web server and an open-source standalone package enhances accessibility, data privacy, and customization for diverse research needs.
  • trRosettaRNA facilitates advancements in understanding RNA structure-function relationships and enables the development of new bioinformatics tools.