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

Sizhe Qiu1, Bozhen Hu2,3, Jing Zhao4,5

  • 1Department of Engineering Science, University of Oxford, Parks Road, OX1 3PJ, Oxford, United Kingdom.

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A new deep learning model, Seq2Topt, accurately predicts enzyme optimal temperature using only protein sequences. This tool aids in enzyme mining and computational enzyme design.

Keywords:
attention mechanismdeep learningenzyme optimal temperaturesequence-based predictionthermophilic proteins

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Area of Science:

  • Biochemistry
  • Computational Biology
  • Enzyme Engineering

Background:

  • Enzyme optimal temperature (Topt) is crucial for catalytic activity.
  • Accurate prediction of Topt is essential for enzyme applications.
  • Existing models have limitations in Topt prediction accuracy.

Purpose of the Study:

  • Develop a deep learning predictor for enzyme Topt using protein sequences.
  • Enhance enzyme mining and in-silico enzyme design.
  • Create a versatile prediction platform for enzyme properties.

Main Methods:

  • Developed Seq2Topt, a deep learning model utilizing protein sequences.
  • Employed multi-head attention to identify key protein regions for Topt.
  • Validated Seq2Topt through case studies on thermophilic enzymes and mutation effects.

Main Results:

  • Seq2Topt achieved superior accuracy in Topt prediction (RMSE = 12.26°C, R2 = 0.57).
  • The model identified critical protein regions influencing Topt.
  • Developed accurate predictors for enzyme optimal pH (Seq2pHopt) and melting temperature (Seq2Tm).

Conclusions:

  • Seq2Topt is a promising computational tool for enzyme discovery and design.
  • The model architecture can be extended to predict other enzyme properties.
  • This work lays the foundation for a comprehensive enzyme property prediction platform.