{
  "abstract": "Hydrogen-deuterium exchange mass spectrometry (HDX-MS) provides powerful insight into protein structure and dynamics, but interpretation of protection patterns at atomic resolution often requires complementary computational modeling. We present PHENOMS, an open-source Python package that integrates molecular dynamics trajectories with HDX-MS data to analyze backbone hydrogen-bond networks by tracking how individual hydrogen bonds and residue-residue contacts form, break, and reorganize throughout the simulations. This residue-level analysis can reveal local structural changes that may be missed by conventional global trajectory metrics. PHENOMS employs a multithreaded, Rust-accelerated computational engine that achieved an average 16-fold speedup (up to 100-fold) over widely used Python-based MD analysis packages in our benchmarks, while retaining individual hydrogen-bond resolution in every trajectory frame. We demonstrate PHENOMS through multiple retrospective case studies using published and in-house datasets, showing that it can recapitulate HDX-MS protection patterns, identify key residues that drive coordinated structural changes, and benchmark the computational efficiency of the approach. With automated quality-control workflows, PHENOMS provides a framework for integrating hydrogen-bond analysis with HDX-MS data or serves as a standalone, high-throughput tool for analyzing MD trajectories for broader applications in protein engineering, drug discovery, and structural biology.",
  "abstract_shown": true,
  "affiliations": [
    "UNC Eshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA",
    "Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.",
    "Segal Cancer Proteomics Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada",
    "Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA",
    "UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
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        0
      ],
      "name": "Brandon Novy"
    },
    {
      "affs": [
        0
      ],
      "name": "Shu-Hang Lin",
      "orcid": "0000-0002-1034-0223"
    },
    {
      "affs": [
        0
      ],
      "name": "Rishabh Dey"
    },
    {
      "affs": [
        1
      ],
      "name": "Brenda Temple"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicole Hajicek"
    },
    {
      "affs": [
        2
      ],
      "name": "Evgeniy V. Petrotchenko"
    },
    {
      "affs": [
        2
      ],
      "name": "Christoph H. Borchers"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "John Sondek"
    },
    {
      "affs": [
        0
      ],
      "name": "Konstantin I. Popov",
      "orcid": "0000-0002-9394-972X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8fqyzewesrz74.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761768",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761768v1.full",
  "id": "8fqyzewesrz74",
  "issns": [
    "2692-8205"
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  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761768v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
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    [
      "heading",
      "Article"
    ]
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  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761768v1.full.pdf",
  "pmcid": "PMC13733869",
  "pmid": "42990235",
  "published": "2026-10-26",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/8fqyzewesrz74.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:20Z",
      "native_id": "10.64898/2026.10.26.761768",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761768v1"
    },
    {
      "first_seen": "2026-11-08T12:23:33Z",
      "native_id": "PMC13733869",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.26.761768"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "PHENOMS: Open-Source Software for Rust-Accelerated Hydrogen-Bond Analysis in Molecular Dynamics Simulations",
  "title_text": "PHENOMS: Open-Source Software for Rust-Accelerated Hydrogen-Bond Analysis in Molecular Dynamics Simulations",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:33Z",
  "url": "https://research.draconitic.com/paper/8fqyzewesrz74",
  "venue": "bioRxiv",
  "versions": []
}