{
  "abstract": "Amyloid-𝛽 42 is a heterogeneous system, widely known as an intrinsically disordered protein, or IDP, sampling a variety of conformations. However, how ensemble redistribution affects the underlying local electronic structure remains less well understood. In this study, classical molecular dynamics simulations are combined with population-aware density functional theory and reduced active-space calculations to compare the LVFFA fragment of the wild-type and Arctic (E22G) variants. Common-space principal component analysis, clustering, and Ramachandran plot analysis depicted distinct trajectory distributions and greater conformational heterogeneity for the E22G trajectory. Population-ranked conformations representing 60.58% of WT and 54.98% of Arctic populations yielded conditional population-weighted B3LYP/def2-SVP HOMO-LUMO separations of 5.81 and 5.95 eV, respectively. The 0.14 eV Arctic–WT shift remained positive across moving-block bootstrap analyses. Fragment expansion altered frontier-orbital ordering, although the spatial character of LVFFA-associated states was preserved. CASCI tested active-space sensitivity, and matched UCCSD-VQE calculations reproduced CAS(4,4) CASCI reference energies for the reduced Hamiltonians. Together, these results demonstrate the importance of population-aware conformational sampling and model-definition sensitivity when relating heterogeneous biomolecular ensembles to quantum-chemical properties.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "kushal patil",
      "orcid": "0009-0003-0211-8109"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/afajr7a0pvvz5.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010287/v1",
  "fulltext_url": null,
  "id": "afajr7a0pvvz5",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010287/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7221552695",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010287/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/afajr7a0pvvz5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010287",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010287/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Conformational Heterogeneity and Local Electronic Structure in Wild-Type and Arctic Amyloid-Β42",
  "title_text": "Conformational Heterogeneity and Local Electronic Structure in Wild-Type and Arctic Amyloid-Β42",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/afajr7a0pvvz5",
  "venue": "ChemRxiv",
  "versions": []
}