{
  "abstract": "Monogenic disorders present a compelling target for drug discovery due to their clear, single-gene etiology. Yet, effective therapies remain scarce, largely because diverse mutation types scattered across a protein obstruct targeted drug design. In this study, we leverage MOGEDO, a curated database of monogenic disorders, to test whether different pathogenic genotypes within a single protein converge on a common molecular mechanism. By clustering MOGEDO proteins into eight functional families and analyzing representative proteins carrying both benign and pathogenic mutations, we integrated molecular dynamics, network analysis, and side-chain entropy metrics. Our findings reveal that distinct pathogenic mutations disrupt the structural and dynamic properties of the wild-type and benign protein through common pathways. By demonstrating that diverse disease-causing mutations manifest a unified pathogenic phenotype, this work provides a framework for designing broad-spectrum therapeutics that target common putative intervention sites rather than individual mutations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physics and Astronomy, College of Science, Clemson University, Clemson, SC 29634, USA",
    "Medical Biophysics Graduate Program, College of Science, Clemson University, Clemson, SC 29634, USA",
    "Institute for Human Genetics, Clemson University, Greenwood, SC 29646, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bikash KC"
    },
    {
      "affs": [
        0
      ],
      "name": "Nirav Modha",
      "orcid": "0009-0005-3895-2677"
    },
    {
      "affs": [
        0
      ],
      "name": "Pitambar Poudel",
      "orcid": "0000-0001-8894-3342"
    },
    {
      "affs": [
        0
      ],
      "name": "Shailesh Kumar Panday",
      "orcid": "0000-0003-3099-8679"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Emil Alexov",
      "orcid": "0000-0001-5346-0156"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8xew9jxkm4gvt.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219432",
  "fulltext_url": null,
  "id": "8xew9jxkm4gvt",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9432",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7223335294",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/8xew9jxkm4gvt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219432",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9432"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Beyond Mutation Diversity: Common Pathogenic Mechanism for Putative Intervention Sites in Monogenic Diseases",
  "title_text": "Beyond Mutation Diversity: Common Pathogenic Mechanism for Putative Intervention Sites in Monogenic Diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/8xew9jxkm4gvt",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}