Rapid Response Antimicrobial Peptide Design Strategy Driven by Meta-Learning for Emerging Drug-Resistant Pathogens
Antimicrobial resistance (AMR) presents a critical global health threat requiring urgent intervention. In order to swiftly respond to and control the spread of emerging drug-resistant bacteria at the onset of their proliferation, our aim is to develop a Rapid Response Antimicrobial Peptide (AMP) design strategy (RR-ADS). This framework addresses the challenge of limited pathogen-specific data by achieving robust generalization from minimal samples by meta-learning and reinforcement learning, optimizing both biocompatibility and efficacy against drug-resistant pathogens. Our model has achieved satisfactory results across multiple evaluation metrics, demonstrating the capability to accurately identify and generate AMPs targeted against drug-resistant bacteria with minimal sample sizes. Within 2 weeks, we successfully designed and experimentally verified AMPs against multidrug-resistant <i>Acinetobacter baumannii</i>, achieving a 93.3% positive rate. RR-ADS has effectively demonstrated the potential of meta-learning in tasks involving bioactive peptides and holds promise as an effective alternative measure to address infectious disease public health emergencies.
Authors
- Jinhui Tian (ORCID: https://orcid.org/0000-0002-7082-3569)
- Wenjin Yan
- Jian Han (ORCID: https://orcid.org/0000-0001-5687-6456)
- Lianhua Wei (ORCID: https://orcid.org/0009-0008-9984-1382)
- Jinqi Huang (ORCID: https://orcid.org/0000-0002-5961-6841)
- Ruya Li
- Rong Xia (ORCID: https://orcid.org/0000-0002-2463-6340)
- Yongshui Fu (ORCID: https://orcid.org/0000-0002-2199-2980)
- Yunxiang Yu (ORCID: https://orcid.org/0009-0008-4149-1412)
- Xinlu Ren
- Shilin Xu
- Mengyun Gu
- Zhou Zhang (ORCID: https://orcid.org/0009-0007-9193-9193)
Institutions
- Gansu Provincial Hospital (CN)
- Guangzhou First People's Hospital (CN)
- Affiliated Hospital of Guangdong Medical College Hospital (CN)
- Lanzhou University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c00188
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Basic and Applied Basic Research Foundation of Guangdong Province