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PreprintCC BYChemRxiv

Specific Recognition of RNA Tetraloop in Tertiary Interactions of RNA

  • Uddipan Bhattacharya1,2
  • Amal Vijay1,2
  • Arnab Mukherjee1,2,3
  1. 1Department of Chemistry
  2. 2Indian Institute of Science Education and Research
  3. 3Department of Data Science
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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.

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Cite

BibTeXRIS
BibTeX
@misc{bhattacharya2026specific,
  title = {{Specific Recognition of RNA Tetraloop in Tertiary Interactions of RNA}},
  author = {Uddipan Bhattacharya and Amal Vijay and Arnab Mukherjee},
  howpublished = {ChemRxiv},
  year = {2026},
  month = aug,
  doi = {10.26434/chemrxiv.15008054/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008054/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Specific Recognition of RNA Tetraloop in Tertiary Interactions of RNA
AU  - Uddipan Bhattacharya
AU  - Amal Vijay
AU  - Arnab Mukherjee
PY  - 2026
DA  - 2026/08/30
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008054/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008054/v1
AB  - 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.
ER  -