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Deep-learning based bioactive peptides generation and screening against Xanthine oxidase

Zhang, H.; Saravanan, K. M.; Zhang, J. Z. H.; Wu, X.

2023-01-13 bioinformatics
10.1101/2023.01.11.523536 bioRxiv
Show abstract

In our previous work, we have developed LSTM_Pep to generate de novo potential active peptides by finetuning with known active peptides and developed DeepPep to effectively identify protein-peptide interaction. Here, we have combined LSTM_Pep and DeepPep to successfully obtained an active de novo peptide (ARG-ALA-PRO-GLU) of Xanthine oxidase (XOD) with IC50 value of 3.76mg/mL, and XOD inhibitory activity of 64.32%. Consistent with the experiment result, the peptide ARG-ALA-PRO-GLU has the highest DeepPep score, this strongly supports that we can generate de novo potential active peptides by finetune training LSTM_Pep over some known active peptides and identify those active peptides by DeepPep effectively. Our work sheds light on the development of deep learning-based methods and pipelines to effectively generate and obtain bioactive peptides with a specific therapeutic effect and showcases how artificial intelligence can help discover de novo bioactive peptides that can bind to a particular target.

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