Kinetics of escape of ssDNA molecules from α-hemolysin nanopores: a dynamic disorder study

Abstract

Experimental studies of the escape events of single-stranded DNA (ssDNA) molecules from the membrane embedded α-hemolysin nanopores exhibited the non-exponential kinetics. The data for homopolymers of adenine (dA27) and cytosine (dC27) revealed the profound influence of the sequence dependent DNA–pore interactions and the applied potentials on the escape kinetics. The non-exponential behavior is a signature of the presence of disorder in biochemical reactions. Here, we rationalize the experimental results with a dynamic disorder approach based on Zwanzig’s fluctuating bottleneck (FB) model as a general mechanism where the rate of the reaction is controlled by the passage of a molecule through the cross-sectional area of the vestibule of the α-hemolysin channel (the bottleneck). The stochastic fluctuations of the radius of the latter is represented by the fluctuations of the intersegment distance of a Rouse chain, the dynamics of which is described using a non-Markovian generalized Langevin equation with a memory kernel and Gaussian colored noise. Our analytical results essentially capture the effects of underlying energetics due to the sequence-dependent nature and applied potentials in reproducing the measured survival probabilities for dA27 and dC27 in an excellent way, thereby validating the application of a simple coarse-grained theory to address the thermal escape of biopolymers from bionanopores.