Learning deep representations of enzyme thermal adaptation

Gang Li; Filip Buric; Jan Zrimec; Sandra Viknander; Jens B Nielsen; Aleksej Zelezniak; Martin Engqvist

doi:10.1002/pro.4480

Learning deep representations of enzyme thermal adaptation
Journal article, 2022

Temperature is a fundamental environmental factor that shapes the evolution of organisms. Learning thermal determinants of protein sequences in evolution thus has profound significance for basic biology, drug discovery, and protein engineering. Here, we use a data set of over 3 million BRENDA enzymes labeled with optimal growth temperatures (OGTs) of their source organisms to train a deep neural network model (DeepET). The protein-temperature representations learned by DeepET provide a temperature-related statistical summary of protein sequences and capture structural properties that affect thermal stability. For prediction of enzyme optimal catalytic temperatures and protein melting temperatures via a transfer learning approach, our DeepET model outperforms classical regression models trained on rationally designed features and other deep-learning-based representations. DeepET thus holds promise for understanding enzyme thermal adaptation and guiding the engineering of thermostable enzymes.

deep neural networks

bioinformatics

enzyme catalytic temperatures

protein thermostability

transfer learning

optimal growth temperatures