Maximizing RNA folding rates: A balancing act

D. Thirumalai, Sarah A. Woodson

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Large ribozymes typically require very long times to refold into their active conformation in vitro, because the RNA is easily trapped in metastable misfolded structures. Theoretical models show that the probability of misfolding is reduced when local and long-range interactions in the RNA are balanced. Using the folding kinetics of the Tetrahymena ribozyme as an example, we propose that folding rates are maximized when the free energies of forming independent domains are similar to each other. A prediction is that the folding pathway of the ribozyme can be reversed by inverting the relative stability of the tertiary domains. This result suggests strategies for optimizing ribozyme sequences for therapeutics and structural studies.

Original languageEnglish (US)
Pages (from-to)790-794
Number of pages5
Issue number6
StatePublished - Jun 2000
Externally publishedYes


  • Group I intron
  • RNA folding
  • RNA structure
  • Ribozyme

ASJC Scopus subject areas

  • Molecular Biology


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