Deep Learning-Based Bioactive Therapeutic Peptide Generation and Screening

Haiping Zhang, Konda Mani Saravanan, Yanjie Wei, Yang Jiao, Yang Yang, Yi Pan, Xuli Wu, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review


Many bioactive peptides demonstrated therapeutic effects over complicated diseases, such as antiviral, antibacterial, anticancer, etc. It is possible to generate a large number of potentially bioactive peptides using deep learning in a manner analogous to the generation of de novo chemical compounds using the acquired bioactive peptides as a training set. Such generative techniques would be significant for drug development since peptides are much easier and cheaper to synthesize than compounds. Despite the limited availability of deep learning-based peptide-generating models, we have built an LSTM model (called LSTM_Pep) to generate de novo peptides and fine-tuned the model to generate de novo peptides with specific prospective therapeutic benefits. Remarkably, the Antimicrobial Peptide Database has been effectively utilized to generate various kinds of potential active de novo peptides. We proposed a pipeline for screening those generated peptides for a given target and used the main protease of SARS-COV-2 as a proof-of-concept. Moreover, we have developed a deep learning-based protein-peptide prediction model (DeepPep) for rapid screening of the generated peptides for the given targets. Together with the generating model, we have demonstrated that iteratively fine-tuning training, generating, and screening peptides for higher-predicted binding affinity peptides can be achieved. Our work sheds light on developing 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.

Original languageEnglish (US)
Pages (from-to)835-845
Number of pages11
JournalJournal of Chemical Information and Modeling
Issue number3
StatePublished - Feb 13 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Computer Science Applications
  • Library and Information Sciences


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