{
  "abstract": "GNRA tetraloops are ubiquitous RNA motifs that drive tertiary folding through tetraloop–receptor (TL–TLR) interactions. However, the mechanisms underlying their ion-dependent stabilization and mutational responses remain unclear. In this study, we performed atomistic molecular dynamics simulations of a minimal TL–TLR system containing a canonical GAAA tetraloop and a GAGA (A48G) mutant. Unbiased simulations combined with time-lagged independent component analysis (TICA) identify slow collective modes governing loop–receptor opening and closing, revealing Mg2+-dependent changes in the conformational ensemble. Enhanced sampling along these modes yields free-energy landscapes that describe Mg2+-mediated stabilization for the wild type. The A48G mutation, however, reshapes the landscape and stabilizes a competing non-native folded state, lowering the unfolding free-energy barrier relative to the wild type in the presence of Mg2+. These results provide an atomistic framework for understanding how divalent ions and sequence variations modulate RNA tertiary recognition and folding pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry",
    "Indian Institute of Science Education and Research",
    "Department of Data Science"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Uddipan Bhattacharya"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Amal Vijay"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Arnab Mukherjee",
      "orcid": "0000-0001-5691-6120"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/46tg9d7s2mzrm.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008054/v1",
  "fulltext_url": null,
  "id": "46tg9d7s2mzrm",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008054/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",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7204808395",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-30",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/46tg9d7s2mzrm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008054",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008054/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA and protein synthesis mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Specific Recognition of RNA Tetraloop in Tertiary Interactions of RNA",
  "title_text": "Specific Recognition of RNA Tetraloop in Tertiary Interactions of RNA",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/46tg9d7s2mzrm",
  "venue": "ChemRxiv",
  "versions": []
}