Orientation-dependent interactions of DNA with an alpha-hemolysin channel

We present experimental and theoretical results on the voltage-dependent escape dynamics of DNA hairpins of different orientations threaded into an alpha -hemolysin channel. Using a coarse-grained formulation, we map the motion of the polymer in the pore to that of a biased single-particle random walk along the translocation coordinate. By fitting the escape probability distributions obtained from theory to experimental data, we extract the voltage-dependent diffusion constants and bias-induced velocities. Using our two-parameter theory, we obtain excellent agreement with experimentally measured escape time distributions. Further, we find that the ratio of mean escape times for hairpins of different orientations is strongly voltage dependent, with the ratio of 3' - to 5' -threaded DNA decreasing from approximately 1.7 to approximately 1 with increasing assisting voltages V(a) . We also find that our model describes 5' -threaded DNA escape extremely well, while providing inadequate fits for 3' escape. Finally, we find that the escape times for both orientations are equal for high assisting voltages, suggesting that the interactions of DNA with the alpha -hemolysin channel are both orientation and voltage dependent.