D. Thirumalai et al., KINETIC PARTITIONING MECHANISM AS A UNIFYING THEME IN THE FOLDING OF BIOMOLECULES, Theoretical chemistry accounts, 96(1), 1997, pp. 14-22
We describe a unified approach to describe the kinetics of protein and
RNA folding. The underlying conceptual basis for this framework relie
s 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 n
ative basin of attraction (NEA), several competing basins of attractio
n. A rough FES results in direct and indirect pathways to the NBA, i.e
., a kinetic partitioning mechanism (KPM). The KPM leads to a foldabil
ity principle according to which fast folding sequences are characteri
zed by the folding transition temperature T-F being close to the colla
pse transition temperature T-theta, at which a transition from the ran
dom coil to the compact structure takes place. Biomolecules with T-the
ta approximate to T-F, such as small proteins and tRNAs, are expected
to fold rapidly with two-state kinetics. Estimates for the multiple ti
me scales in KPM are also given. We show that experiments on proteins
and RNA can be understood semi-quantitatively in terms of the KPM.