{
  "abstract": "Sidechain packing is a critical stage in protein folding, with direct implications for structure-based drug discovery. Google DeepMind's tool, AlphaFold2, predicts protein backbone reliably but sidechain positioning less accurately. Recovering the lowest-energy rotamer assignment over a fixed backbone is NP-hard. We present a hybrid quantum-classical pipeline that repacks sidechains on the AlphaFold backbone using the Quantum Approximate Optimisation Algorithm (QAOA), encoding the one- and two-body energies as a quadratic unconstrained binary optimisation (QUBO) problem. We introduce a constraint-preserving ansatz, pairing a W-state initialisation with a cyclic XY ring mixer, that enforces one-hot rotamer validity without penalty terms while keeping two-qubit gate scaling linear in the rotamer count. We also define an asymptotic shot-scaling metric, measured against the experimentally resolved conformation, that fixes optimiser quality independently of the baseline; its fitted growth stays below the classical exhaustive-search rate at moderate rotamer flexibility. Evaluated on bovine pancreatic trypsin inhibitor (5PTI) across high- and moderate AlphaFold-confidence regions, the pipeline lowers conformational energy against the AlphaFold baseline.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2609.31077",
  "author_total": 4,
  "authors": [
    {
      "name": "Sebastian O. M. Stewart"
    },
    {
      "name": "Nick Chancellor"
    },
    {
      "name": "Jonte R Hance"
    },
    {
      "name": "Ittoop Vergheese Puthoor"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0peqr1t8rqn8q.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2609.31077",
  "fulltext_url": null,
  "id": "0peqr1t8rqn8q",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2609.31077",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "quant-ph"
    ],
    [
      "openalex",
      "1702|Quantum Computing Algorithms and Architecture"
    ]
  ],
  "openalex": "W7214585005",
  "pdf_url": "https://arxiv.org/pdf/2609.31077",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0peqr1t8rqn8q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:52Z",
      "native_id": "2609.31077",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2609.31077"
    }
  ],
  "subjects": [
    {
      "field": "physics",
      "origin": "arxiv:quant-ph",
      "subfield": "quantum"
    }
  ],
  "title": "Quantum Approximate Optimisation Algorithm for Protein Sidechain Packing",
  "title_text": "Quantum Approximate Optimisation Algorithm for Protein Sidechain Packing",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:52Z",
  "url": "https://research.draconitic.com/paper/0peqr1t8rqn8q",
  "venue": "arXiv",
  "versions": []
}