Analyzing the biopolymer folding rates and pathways using kinetic cluster method.

A kinetic cluster method enables us to analyze biopolymer folding kinetics with discrete rate-limiting steps by classifying biopolymer conformations into pre-equilibrated clusters. The overall folding kinetics is determined by the intercluster transitions. Due to the complex energy landscapes of biopolymers, the intercluster transitions have multiple pathways and can have kinetic intermediates (local free-energy minima) distributed on the intercluster pathways. We focus on the RNA secondary structure folding kinetics. The dominant folding pathways and the kinetic partitioning mechanism can be identified and quantified from the rate constants for different intercluster pathways. Moreover, the temperature dependence of the folding rate can be analyzed from the interplay between the stabilities of the on-pathway (nativelike) and off-pathway (misfolded) conformations and from the kinetic partitioning between different intercluster pathways. The predicted folding kinetics can be directly tested against experiments.