{
  "abstract": "Multivalent ions bind to proteins to control many biological processes. Molecular simulations can effectively supplement experiments to resolve underlying mechanisms, but suffer from reliability and feasibility issues in describing ion-protein binding in the condensed phase. Here we present a molecular mechanics based generalizable solution to this long-standing challenge. Using the divalent Mg 2+ as a model, we demonstrate that our approach yields unprecedented accuracy in describing its binding to proteins in solution – compared to high level quantum mechanics, the mean error in local interaction energies is 0.5%, and the binding modes and binding free energies match experiment. Our study also shows that key to achieving this accuracy requires a delicate balance between the large repulsive and attractive forces at short distances near ions for which explicit modeling of polarization is essential. Overall, our work lays foundation for future development of molecular simulation methods for ions and opens the way to quantitatively study Mg-dependent mechanisms in hundreds of enzymes and proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biosciences, University of South Florida, 4202 E. Fowler Ave., Tampa, USA, FL-33620",
    "Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., Budapest, Hungary, H-1111",
    "HUN-REN-BME Quantum Chemistry Research Group, Műegyetem rkp. 3., Budapest, Hungary, H-1111",
    "MTA-BME Lendület Quantum Chemistry Research Group, Műegyetem rkp. 3., Budapest, Hungary, H-1111",
    "Department of physics, University of South Florida, 4202 E. Fowler Ave., Tampa, Florida, United States, 33620"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Giorgio Schillaci",
      "orcid": "0009-0009-0068-4602"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian Mélendez Delgado"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew Saunders"
    },
    {
      "affs": [
        0
      ],
      "name": "Irene Arias Gutierrez"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Péter R. Nagy"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Sameer Varma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2kkc5nncz5ms0.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009072/v1",
  "fulltext_url": null,
  "id": "2kkc5nncz5ms0",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009072/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",
      "3107|Advanced Chemical Physics Studies"
    ]
  ],
  "openalex": "W7213541568",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/2kkc5nncz5ms0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15009072",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009072/v1"
    }
  ],
  "subjects": [
    {
      "field": "physics",
      "origin": "openalex:3107|Advanced Chemical Physics Studies",
      "subfield": "amo"
    }
  ],
  "title": "Accurate modeling of ion-protein binding in solution: molecular mechanics force field innovation and validation on Mg2+",
  "title_text": "Accurate modeling of ion-protein binding in solution: molecular mechanics force field innovation and validation on Mg2+",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/2kkc5nncz5ms0",
  "venue": "ChemRxiv",
  "versions": []
}