Back

VIPER: A General Model for Prediction of Enzyme Substrates

Campbell, M. J.

2024-12-16 bioinformatics
10.1101/2024.06.21.599972 bioRxiv
Show abstract

Enzymes, natures catalysts, possess remarkable properties such as high stereo-, regio-, and chemo-specificity. These properties allow enzymes to greatly simplify complex synthetic processes, resulting in improved yields and reduced manufacturing costs compared to traditional chemical methods. However, the lack of experimental characterization of enzyme substrates, with only a few thousand out of tens of millions of known enzymes in Uniprot having annotated substrates, severely limits the ability of chemists to repurpose enzymes for industrial applications. Previous machine learning models aimed at predicting enzyme substrates have been hampered by poor generalization to new substrates. Here, we introduce VIPER (Virtual Interaction Predictor for Enzyme Reactivity), a model that achieves an average 30% improvement over the previous state-of-the-art model (ProSmith) in reaction prediction for unseen substrates. Furthermore, we reveal flaws in previous enzyme-substrate reaction datasets, and introduce a novel high-quality enzyme-substrate reaction dataset to alleviate these issues.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.