KINETIC PARTITIONING MECHANISM AS A UNIFYING THEME IN THE FOLDING OF BIOMOLECULES

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.