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AI-guided few-shot inverse design of HDP-mimicking polymers against drug-resistant bacteria

Author

Listed:
  • Tianyu Wu

    (East China University of Science and Technology)

  • Min Zhou

    (East China University of Science and Technology)

  • Jingcheng Zou

    (East China University of Science and Technology)

  • Qi Chen

    (East China University of Science and Technology)

  • Feng Qian

    (East China University of Science and Technology)

  • Jürgen Kurths

    (Potsdam Institute for Climate Impact Research (PIK)
    Humboldt-Universität zu Berlin
    Fudan University)

  • Runhui Liu

    (East China University of Science and Technology
    East China University of Science and Technology)

  • Yang Tang

    (East China University of Science and Technology)

Abstract

Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives to antibiotics and have large-scale untapped potential. Artificial intelligence (AI) exhibits promising performance on large-scale chemical-content design, however, existing AI methods face difficulties on scarcity data in each family of HDP-mimicking polymers ( 105), and multi-constraints on properties and structures when exploring high-dimensional polymer space. Herein, we develop a universal AI-guided few-shot inverse design framework by designing multi-modal representations to enrich polymer information for predictions and creating a graph grammar distillation for chemical space restriction to improve the efficiency of multi-constrained polymer generation with reinforcement learning. Exampled with HDP-mimicking β-amino acid polymers, we successfully simulate predictions of over 105 polymers and identify 83 optimal polymers. Furthermore, we synthesize an optimal polymer DM0.8iPen0.2 and find that this polymer exhibits broad-spectrum and potent antibacterial activity against multiple clinically isolated antibiotic-resistant pathogens, validating the effectiveness of AI-guided design strategy.

Suggested Citation

  • Tianyu Wu & Min Zhou & Jingcheng Zou & Qi Chen & Feng Qian & Jürgen Kurths & Runhui Liu & Yang Tang, 2024. "AI-guided few-shot inverse design of HDP-mimicking polymers against drug-resistant bacteria," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50533-4
    DOI: 10.1038/s41467-024-50533-4
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