Geometric deep learning assists protein engineering. Opportunities and Challenges

Fuente: arXiv
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Auteurs principaux: García-Vinuesa, Julián, Rojas, Jorge, Soto-García, Nicole, Martínez, Nicolás, Alvarez-Saravia, Diego, Uribe-Paredes, Roberto, Davari, Mehdi D., Conca, Carlos, Asenjo, Juan A., Medina-Ortiz, David
Format: Preprint
Publié: 2025
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author García-Vinuesa, Julián
Rojas, Jorge
Soto-García, Nicole
Martínez, Nicolás
Alvarez-Saravia, Diego
Uribe-Paredes, Roberto
Davari, Mehdi D.
Conca, Carlos
Asenjo, Juan A.
Medina-Ortiz, David
author_facet García-Vinuesa, Julián
Rojas, Jorge
Soto-García, Nicole
Martínez, Nicolás
Alvarez-Saravia, Diego
Uribe-Paredes, Roberto
Davari, Mehdi D.
Conca, Carlos
Asenjo, Juan A.
Medina-Ortiz, David
contents Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled relevant advances, they remain limited by the complexity of sequence space and the cost of experimental validation. Geometric deep learning addresses these limitations by operating on non-Euclidean domains, capturing spatial, topological, and physicochemical features essential to protein function. This perspective outlines the current applications of GDL across stability prediction, functional annotation, molecular interaction modeling, and de novo protein design. We highlight recent methodological advances in model generalization, interpretability, and robustness, particularly under data-scarce conditions. A unified framework is proposed that integrates GDL with explainable AI and structure-based validation to support transparent, autonomous design. As GDL converges with generative modeling and high-throughput experimentation, it is emerging as a central technology in next-generation protein engineering and synthetic biology.
format Preprint
id arxiv_https___arxiv_org_abs_2506_16091
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Geometric deep learning assists protein engineering. Opportunities and Challenges
García-Vinuesa, Julián
Rojas, Jorge
Soto-García, Nicole
Martínez, Nicolás
Alvarez-Saravia, Diego
Uribe-Paredes, Roberto
Davari, Mehdi D.
Conca, Carlos
Asenjo, Juan A.
Medina-Ortiz, David
Quantitative Methods
Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled relevant advances, they remain limited by the complexity of sequence space and the cost of experimental validation. Geometric deep learning addresses these limitations by operating on non-Euclidean domains, capturing spatial, topological, and physicochemical features essential to protein function. This perspective outlines the current applications of GDL across stability prediction, functional annotation, molecular interaction modeling, and de novo protein design. We highlight recent methodological advances in model generalization, interpretability, and robustness, particularly under data-scarce conditions. A unified framework is proposed that integrates GDL with explainable AI and structure-based validation to support transparent, autonomous design. As GDL converges with generative modeling and high-throughput experimentation, it is emerging as a central technology in next-generation protein engineering and synthetic biology.
title Geometric deep learning assists protein engineering. Opportunities and Challenges
topic Quantitative Methods
url https://arxiv.org/abs/2506.16091