{
  "abstract": "How well do general-purpose molecular mechanics force fields predict solvent–water partition coefficients for drug-like molecules? To answer this question, we performed massively parallel expanded ensemble free energy calculations using distributed computing to evaluate two widely used force fields—GAFF 2.1 and OpenFF 2.0—across a diverse set of 70 molecules and solvents (chloroform, dodecane, octanol and toluene). We find both force fields have comparable accuracy, with predicted transfer free energies having mean unsigned errors (MUEs) below 2 kcal/mol in nearly all cases. Our results also reveal systematic error, likely due to the known deficiencies of fixed-charge force fields. We expect that this dataset and our approach to systematic evaluation using distributed computing may be useful toward future efforts in force field validation and parameterization.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Steven R. Goold"
    },
    {
      "name": "Vincent A. Voelz",
      "orcid": "0000-0002-1054-2124"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/51b2xyzv1tf3v.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010089/v1",
  "fulltext_url": null,
  "id": "51b2xyzv1tf3v",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010089/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": "W7220992525",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010089/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/51b2xyzv1tf3v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010089",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010089/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Expanded ensemble predictions of solvent–water partition coefficients for drug-like molecules using OpenFF 2.0 and GAFF 2.1",
  "title_text": "Expanded ensemble predictions of solvent–water partition coefficients for drug-like molecules using OpenFF 2.0 and GAFF 2.1",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/51b2xyzv1tf3v",
  "venue": "ChemRxiv",
  "versions": []
}