{
  "abstract": "Antimicrobial peptides (AMPs) are a promising solution to antimicrobial resistance, yet generative models for their design cannot control the physicochemical properties and motifs that shape activity and selectivity. Here, we present OmegAMP, a conditional diffusion framework controlling net charge, mean hydrophobicity, and sequence length, supporting de novo, analog, and motif-guided design. Across 204 wet-lab characterized peptides, de novo generation yielded antimicrobials with broad activity against multidrug-resistant Gram-negative isolates. Analog generation converted six inactive prototypes into antimicrobials, with the prototype determining each analog's membrane-disruption mode and mammalian-cell safety. Motif-guided analog generation preserved lipopolysaccharide engagement of active prototypes, and a redesigned non-antimicrobial leucine zipper acquired antimicrobial activity while retaining DNA-perturbing character in vitro. In murine skin and thigh infection models, leads reduced bacterial burden, with a motif-guided DNA-perturbing lead matching the fluoroquinolone control systemically. OmegAMP opens a programmable route to new peptide antibiotics whose mechanism and safety follow from the chosen prototype.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of AI for Health, Helmholtz Zentrum Munich"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "P. Szymczak"
    },
    {
      "name": "M. D. T. Torres"
    },
    {
      "name": "D. Soares"
    },
    {
      "name": "L. Hetzel"
    },
    {
      "name": "B. Puczko-Szymanski"
    },
    {
      "name": "S. Jegelka"
    },
    {
      "name": "S. Günnemann"
    },
    {
      "name": "F. J. Theis"
    },
    {
      "name": "C. de la Fuente-Nunez"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Szczurek"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b2fffd422zysv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.747572",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.747572v1.full",
  "id": "b2fffd422zysv",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.747572v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "2404|Antimicrobial Peptides and Activities"
    ]
  ],
  "openalex": "W7205009879",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.747572v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b2fffd422zysv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:27Z",
      "native_id": "10.64898/2026.09.01.747572",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.747572v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Designing antimicrobials with programmable mechanism and safety",
  "title_text": "Designing antimicrobials with programmable mechanism and safety",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:27Z",
  "url": "https://research.draconitic.com/paper/b2fffd422zysv",
  "venue": "bioRxiv",
  "versions": []
}