Master equation approach to finding the rate-limiting steps in biopolymer folding.

A master equation approach is developed to find the rate-limiting steps in biopolymer folding, where the folding kinetics is described as a linear combination of basic kinetic modes determined from the eigenvalues and eigenvectors of the rate matrix. Because the passage of a rate-limiting step is intrinsically related to the folding speed, it is possible to probe and to identify the rate-limiting steps through the folding from different unfolded initial conformations. In a master equation approach, slow and fast folding speeds are directly correlated to the large and small contributions of the (rate-limiting) slow kinetic modes. Because the contributions from the slow modes can be computed from the corresponding eigenvectors, the rate-limiting steps can be identified from the eigenvectors of the slow modes. Our rate-limiting searching method has been tested for a simplified hairpin folding kinetics model, and it may provide a general transition state searching method for biopolymer folding.