Accurately predicting enzyme functions through geometric graph learning on ESMFold-predicted structures

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Song, Y
Yuan, Q
Chen, S
Zeng, Y
Zhao, H
Yang, Y
Griffith University Author(s)
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2024
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Abstract

Enzymes are crucial in numerous biological processes, with the Enzyme Commission (EC) number being a commonly used method for defining enzyme function. However, current EC number prediction technologies have not fully recognized the importance of enzyme active sites and structural characteristics. Here, we propose GraphEC, a geometric graph learning-based EC number predictor using the ESMFold-predicted structures and a pre-trained protein language model. Specifically, we first construct a model to predict the enzyme active sites, which is utilized to predict the EC number. The prediction is further improved through a label diffusion algorithm by incorporating homology information. In parallel, the optimum pH of enzymes is predicted to reflect the enzyme-catalyzed reactions. Experiments demonstrate the superior performance of our model in predicting active sites, EC numbers, and optimum pH compared to other state-of-the-art methods. Additional analysis reveals that GraphEC is capable of extracting functional information from protein structures, emphasizing the effectiveness of geometric graph learning. This technology can be used to identify unannotated enzyme functions, as well as to predict their active sites and optimum pH, with the potential to advance research in synthetic biology, genomics, and other fields.

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Nature Communications

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15

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1

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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived fromthis article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Enzymes

Biochemistry and cell biology

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Song, Y; Yuan, Q; Chen, S; Zeng, Y; Zhao, H; Yang, Y, Accurately predicting enzyme functions through geometric graph learning on ESMFold-predicted structures, Nature Communications, 2024, 15 (1), pp. 8180

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