{
  "abstract": "Peptides at biological interfaces often encode function through preferential compatibility with chemical environments rather than through binding to a single molecular target. We report a physically motivated, knowledge-based Hamiltonian for programming such preferences in α-helical peptides. The model maps amino-acid sequences onto a normalized energy landscape that combines helix propensity, local sequence context, residue contacts, solvent exposure, membrane charge coupling, and electrostatic screening. Random-reference Z-scores place different lengths, residue sets, and environments on a common scale. In homogeneous benchmarks, the Hamiltonian separates experimentally characterized alanine-rich Glu/Lys water-soluble helices from WALP/GWALP transmembrane model helices. In interfacial benchmarks, it recognizes canonical membrane-active antimicrobial peptides as preferentially stabilized at anionic interfaces over neutral, cationic, aqueous, and apolar alternatives, while rejecting non-antimicrobial helical controls. The same score generates sequence libraries for environment-specific compatibility, polar-apolar robustness, and one-vs-rest anionic selectivity. Low-energy ensembles display amphipathic segregation, charge regulation, and hydrophobicity periodicity at sequence separations of 3 and 4 residues, linking the designed sequences to interpretable chemical organization. Because the objective is a discrete Hamiltonian, it can be explored by exact search, classical heuristics, and binary-encoded quantum-compatible workflows without changing the scoring function. This framework provides a transparent route to design α-helical peptides whose environmental preferences are specified directly in the molecular objective.",
  "abstract_shown": true,
  "affiliations": [
    "Departamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, Santiago de CompostelaE-15782, Spain.",
    "Organic Chemistry Department, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, Campus Vida s/n, Santiago de CompostelaE-15782, Spain."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniel Conde-Torres"
    },
    {
      "affs": [
        1
      ],
      "name": "Rebeca García-Fandiño",
      "orcid": "0000-0002-5274-3928"
    },
    {
      "affs": [
        0
      ],
      "name": "Ángel Piñeiro",
      "orcid": "0000-0001-9350-8468"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fn7jvhqsyhw3e.bib",
  "cited_by": 1,
  "doi": "10.1021/acs.jctc.6c01278",
  "fulltext_url": "https://europepmc.org/articles/PMC13602920",
  "id": "fn7jvhqsyhw3e",
  "issns": [
    "1549-9618",
    "1549-9626"
  ],
  "landing_url": "https://europepmc.org/article/MED/42917473",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7211924386",
  "pdf_url": "https://europepmc.org/articles/PMC13602920?pdf=render",
  "pmcid": "PMC13602920",
  "pmid": "42917473",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fn7jvhqsyhw3e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42917473",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42917473"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Environment-Conditioned Design of α-Helical Peptides.",
  "title_text": "Environment-Conditioned Design of α-Helical Peptides.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/fn7jvhqsyhw3e",
  "venue": "Journal of chemical theory and computation",
  "versions": []
}