A pr 1 99 7 Kinetic Partitioning Mechanism as a Unifying Theme in the Folding of Biomolecules

We describe a unified approach to describe the kinetics of folding of proteins and RNA. The underlying conceptual basis for this framework relies on the notion that biomolecules are topologically frustrated due to the polymeric nature and due to the presence of conflicting energies. As a result the free energy surface that has, in addition to the native basin of attraction (NBA), several competing basins of attraction. A rough free energy surface 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 T F being close to the collapse transition temperature T θ , at which a transition from the random coil to the compact structure takes place. Biomolecules with T θ ≈ T F , 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 kinetic partitioning mechanism.