Seq2Topt: a sequence-based deep learning predictor of enzyme optimal temperature.

Abstract

An accurate deep learning predictor is needed for enzyme optimal temperature (${T}_{opt}$), which quantitatively describes how temperature affects the enzyme catalytic activity. In comparison with existing models, a new model developed in this study, Seq2Topt, reached a superior accuracy on ${T}_{opt}$ prediction just using protein sequences (RMSE = 12.26°C and R2 = 0.57), and could capture key protein regions for enzyme ${T}_{opt}$ with multi-head attention on residues. Through case studies on thermophilic enzyme selection and predicting enzyme ${T}_{opt}$ shifts caused by point mutations, Seq2Topt was demonstrated as a promising computational tool for enzyme mining and in-silico enzyme design. Additionally, accurate deep learning predictors of enzyme optimal pH (Seq2pHopt, RMSE = 0.88 and R2 = 0.42) and melting temperature (Seq2Tm, RMSE = 7.57 °C and R2 = 0.64) were developed based on the model architecture of Seq2Topt, suggesting that the development of Seq2Topt could potentially give rise to a useful prediction platform of enzymes.