Kinetic partitioning mechanism as a unifying theme in the folding of biomolecules

D. Thirumalai, D. K. Klimov, S. A. Woodson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


We describe a unified approach to describe the kinetics of protein and RNA folding. The underlying conceptual basis for this framework relies on the notion that biomolecules are topologically frustrated due to their polymeric nature and due to the presence of conflicting energies. As a result, the free energy surface (FES) has, in addition to the native basin of attraction (NBA), several competing basins of attraction. A rough FES results in direct and indirect pathways to the NBA, i.e., a kinetic partitioning mechanism (KPM). The KPM leads to a foldability principle according to which fast folding sequences are characterized by the folding transition temperature TF being close to the collapse transition temperature Tθ, at which a transition from the random coil to the compact structure takes place. Biomolecules with Tθ ≈ TF such as small proteins and tRNAs, are expected to fold rapidly with two-state kinetics. Estimates for the multiple time scales in KPM are also given. We show that experiments on proteins and RNA can be understood semi-quantitatively in terms of the KPM.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalTheoretical Chemistry Accounts
Issue number1
StatePublished - Apr 1997


  • Kinetic partitioning mechanism
  • Nucleation collapse
  • RNA folding

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry


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