Exploring the energy landscape of a small RNA hairpin

Hairong Ma, David J. Proctor, Elzbieta Kierzek, Ryszard Kierzek, Philip C. Bevilacqua, Martin Gruebele

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


The energy landscape of a small RNA tetraloop hairpin is explored by temperature jump kinetics and base-substitution. The folding kinetics are single-exponential near the folding transition midpoint Tm. An additional fast phase appears below the midpoint, and an additional slow phase appears above the midpoint. Stem mutation affects the high-temperature phase, while loop mutation affects the low-temperature phase. An adjusted 2-D lattice model reproduces the temperature-dependent phases, although it oversimplifies the structural interpretation. A four-state free energy landscape model is generated based on the lattice model. This model explains the thermodynamics and multiphase kinetics over the full temperature range of the experiments. An analysis of three variants shows that one of the intermediate RNA structures is a stacking-related trap affected by stem but not loop modification, while the other is an early intermediate that forms some stem and loop structure. Even a very fast-folding 8-mer RNA with an ideal tetraloop sequence has a rugged energy landscape, ideal for testing analytical and computational models.

Original languageEnglish (US)
Pages (from-to)1523-1530
Number of pages8
JournalJournal of the American Chemical Society
Issue number5
StatePublished - Feb 8 2006

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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