{
  "abstract": "Understanding protein–ligand interactions based on their electronic states is important for elucidating molecular recognition and supporting structure-based drug discovery. In this study, we performed fragment molecular orbital (FMO) calculations, a quantum chemical approach, for a comprehensive set of experimentally determined protein–ligand complexes derived from BindingDB. Ligand–amino acid residue interactions were quantitatively characterized using inter-fragment interaction energies (IFIEs) and pair interaction energy decomposition analysis (PIEDA), and were compared with molecular mechanics (MM) interaction energies. The comparison revealed residue- and interaction-dependent differences between the FMO and MM descriptions, with particularly distinct behavior for interactions involving aromatic residues. Comprehensive IFIE/PIEDA analysis further revealed characteristic energetic contributions associated with amino acid residue type and ligand charge, including dispersion contributions involving aromatic residues and charge-transfer contributions associated with hydrogen-bonding interactions. A case study of MAPK14 demonstrated that the resulting dataset can identify residue regions commonly involved in ligand recognition and distinguish residue-level interaction patterns among individual ligands. These results provide a systematic quantum chemical perspective on diverse protein–ligand interactions and establish a quantum chemical resource for complementing structural, experimental, and conventional MM-based analyses.",
  "abstract_shown": true,
  "affiliations": [
    "Graduate School of Pharmaceutical Sciences",
    "University of Osaka",
    "Computational Chemistry Business Department, Engineering Technology Business Unit",
    "JSOL Corporation",
    "Department of Applied Chemistry, Graduate School of Engineering",
    "Kyushu University",
    "Graduate School of Information Science and Electrical Engineering"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shuhei Miyakawa",
      "orcid": "0009-0005-6275-5550"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Naoko Konami",
      "orcid": "0009-0003-1683-1511"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ruri Mihata",
      "orcid": "0009-0000-0389-508X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rikuto Osaki"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ayaka Masuda",
      "orcid": "0009-0007-9633-891X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tomoka Taguchi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Toma Miyagishi",
      "orcid": "0009-0006-6357-1021"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Koji Okuwaki",
      "orcid": "0000-0002-4510-5717"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Koichiro Kato",
      "orcid": "0000-0003-4392-8741"
    },
    {
      "affs": [
        6,
        5
      ],
      "name": "Yoshiharu Mori",
      "orcid": "0000-0002-2795-2808"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yu-Shi Tian",
      "orcid": "0000-0002-8988-9453"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daisuke Takaya",
      "orcid": "0000-0001-6020-8151"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kaori Fukuzawa",
      "orcid": "0000-0001-5357-8250"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4m6kdy8b201vy.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009601/v1",
  "fulltext_url": null,
  "id": "4m6kdy8b201vy",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009601/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",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7214724145",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009601/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/4m6kdy8b201vy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009601",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009601/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Comprehensive Quantum Chemical Interaction Analysis of Whole Protein–Ligand Structures in BindingDB Using the Fragment Molecular Orbital Method",
  "title_text": "Comprehensive Quantum Chemical Interaction Analysis of Whole Protein–Ligand Structures in BindingDB Using the Fragment Molecular Orbital Method",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/4m6kdy8b201vy",
  "venue": "ChemRxiv",
  "versions": []
}