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Physics-Informed Neural Networks for Accurate Computational Learning of RNA Elements

Project description

New computational approach to map RNA structures in 3D

Deep learning algorithms have successfully decoded how complex amino acid sequences fold into 3D protein structures. Despite progress in the field, they struggle to map the 3D shapes of RNA molecules. Although the latter dictate how RNA functions and drives diseases, researchers lack the massive datasets needed to train standard AI models. Supported by the Marie Skłodowska-Curie Actions programme, the PINNACLE project aims to develop a novel computational framework to tackle this data scarcity. The proposed framework will combine a highly curated dataset with a neural network that learns the fundamental physical and biochemical laws governing RNA folding, rather than relying on raw data alone. This open-source tool will help reduce data dependency, ultimately accelerating RNA-based drug discovery.

Objective

Ribonucleic acid (RNA) molecules are central to cellular function and disease, with their biological roles being intrinsically linked to their complex three-dimensional (3D) structures. However, a significant gap exists between the number of known RNA sequences and experimentally determined structures. This data scarcity severely hampers the application of state-of-the-art deep learning methods, which have revolutionized protein structure prediction but fail to generalize for RNA due to their reliance on vast datasets.

The PINNACLE (Physics-Informed Neural Networks for Accurate Computational Learning of RNA Elements) project will address this fundamental challenge through a novel, physics-aware computational framework. The project has two primary objectives: 1) To construct and disseminate a high-quality, FAIR-compliant, and systematically curated dataset of RNA 3D structures, augmented with molecular simulations to capture molecular flexibility and rare interactions. 2) To develop and validate a novel Bayesian Physics-Informed Neural Network (B-PINN) that directly embeds the fundamental physical and biochemical laws governing RNA folding (e.g. electrostatics, base-stacking, torsional constraints) into the model's learning process.

PINNACLE will reduce the dependency on large training sets, improve generalization to novel RNA families, and provide robust uncertainty quantification for its predictions - a critical feature for guiding experimental research. This action will deliver a transformative open-source tool for the scientific community, accelerating research in RNA biology and the development of RNA-based therapeutics. Furthermore, this interdisciplinary training will equip the researcher with a unique skill-set at the intersection of AI, biophysics, and bioinformatics, providing a robust foundation for a future independent research career.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution
€ 263 393,28
Address
NORREGADE 10
1165 KOBENHAVN
Denmark
Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)