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CLIMBS: assessing Carbohydrate-Protein interactions through a graph neural network classifier using synthetic negative data

Luo, Y.; Parmeggiani, F.

2025-03-05 bioinformatics
10.1101/2025.02.27.640667 bioRxiv
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I.Carbohydrate-protein interactions are essential for biological processes, such as cellular signaling and metabolism, and represent a large pool of untapped targets for diagnostics and therapeutics. However, current design and prediction methods fail to accurately evaluate the affinity and specificity of proteins for carbohydrates such as glucose and galactose. Here, we describe a machine learning classifier, named CLIMBS, as a novel scoring method for protein-carbohydrate interactions and train it on crystal structures and synthetic data from unsuccessfully designed binders, to effectively assess if carbohydrate-protein complexes represent realistic, native like structures. Compared to other methods, CLIMBS has outstanding accuracy, excellent carbohydrate specificity, sub-second runtime per sample, minimal bias towards either negative or positive samples, and can be employed to improve selection of successful docking and design models of carbohydrate-protein complexes.

Published in Journal of Chemical Information and Modeling (predicted rank #1) · training set

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