Early events in RNA folding

D. Thirumalai, Namkyung Lee, Sarah A. Woodson, D. K. Klimov

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


We describe a conceptual framework for understanding the way large RNA molecules fold based on the notion that their free-energy landscape is rugged. A key prediction of our theory is that RNA folding can be described by the kinetic partitioning mechanism (KPM). According to KPM a small fraction of molecules folds rapidly to the native state whereas the remaining fraction is kinetically trapped in a low free-energy non-native state. This model provides a unified description of the way RNA and proteins fold. Single-molecule experiments on Tetrahymena ribozyme, which directly validate our theory, are analyzed using KPM. We also describe the earliest events that occur on microsecond time scales in RNA folding. These must involve collapse of RNA molecules that are mediated by counterion-condensation. Estimates of time scales for the initial events in RNA folding are provided for the Tetrahymena ribozyme.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalAnnual Review of Physical Chemistry
StatePublished - 2001
Externally publishedYes


  • Counterion-condensation
  • Kinetic partitioning mechanism
  • RNA folding pathways
  • Specific and nonspecific collapse
  • Tetrahymena ribozyme

ASJC Scopus subject areas

  • Medicine(all)


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