{
  "abstract": "Ab initio QM/MM molecular dynamics can describe chemical processes accurately, but its practical use is limited by the cost of repeated electronic-structure calculations and by overhead in coupling molecular-dynamics and quantum-chemistry programs. We present QM_eMMa, an open interface that couples AMBER to PySCF/GPU4PySCF while keeping the electronic-structure engine and GPU context active throughout a simulation. The converged electronic density is reused between consecutive MD steps, with automatic recovery through a cold-start SCF calculation when needed. We first optimized the workflow with a GH125 α-mannosidase model. Removing repeated interface overhead increased throughput by approximately 26%. Systematic energy and force comparisons then identified a less expensive numerical setting that retained the accuracy required for MD and increased throughput by a further 23% in independent GH125 simulations. The same protocol enabled stable DFT/MM dynamics of a larger enzymatic QM region containing 115 electronic centers and sustained 145 ps of ab initio well-tempered metadynamics, recovering the principal α-mannose conformational basins observed previously. Finally, a reactive aqueous SN2 benchmark showed that the optimized and stricter protocols gave activation and reaction free energies differing by only 0.73 and 0.01 kcal mol-1, respectively, while the optimized calculation remained faster. QM_eMMa therefore provides a practical open framework for single-GPU DFT/MM dynamics and enhanced sampling, with numerical approximations selected through explicit validation of energies, forces, dynamics, and chemical reactivity.",
  "abstract_shown": true,
  "affiliations": [
    "Computing for Science",
    "Institut Laue-Langevin",
    "Otto-Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6/III, Graz, Austria, A-8010"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Santiago Alonso-Gil",
      "orcid": "0000-0001-7596-8161"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d2dwphp1eh5v6.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009206/v1",
  "fulltext_url": null,
  "id": "d2dwphp1eh5v6",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009206/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3107|Advanced Chemical Physics Studies"
    ]
  ],
  "openalex": "W7213981974",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009206/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/d2dwphp1eh5v6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009206",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009206/v1"
    }
  ],
  "subjects": [
    {
      "field": "physics",
      "origin": "openalex:3107|Advanced Chemical Physics Studies",
      "subfield": "amo"
    }
  ],
  "title": "QM_eMMa: An Open GPU-Accelerated Framework for Ab Initio QM/MM Molecular Dynamics and Enhanced Sampling",
  "title_text": "QM_eMMa: An Open GPU-Accelerated Framework for Ab Initio QM/MM Molecular Dynamics and Enhanced Sampling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/d2dwphp1eh5v6",
  "venue": "ChemRxiv",
  "versions": []
}