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Orientation dependent DNA dynamics

The transport of ssDNA through the ~1.5 nm protein pore alpha-Hemolysin depends not only on DNA sequence, but also on its orientation with respect to the pore. Figure 1 displays the measured "escape" dynamics of poly-adenine molecules from the pore, entered either with their 3′ (red)or their 5′ (green) ends to the cis side of the pore. Clearly the 3′ molecules are retarded. In these experiments the escape of the DNA was measured with no bias voltage.

At first look these results appear to be surprising: If we model the DNA-pore interactions using an asymmetric saw-tooth potential, entering the pore with either the 3′ or the 5′ end corresponds to flipping the direction of the potential energy. but at V=0 the height of the energy barriers in the potential are identical, leading to symmetrical dynamics (Figure 2).

Molecular dynamics (MD) simulations of the system indicate that the asymmetry in the pore and the DNA may result in completely different interaction potential, depending on the way in which the DNA is initially threaded into the pore. The confinement of the ssDNA into the 1.5 nm pore, result in a collective tilt of the bases toward the 5′ end, which in turn interact stronger with the asymmetric pore structure when threaded 3′ first (Figure 3). MD simulations were performed in Klaus Schulten′s group ( in collaboration with Aleksei Aksimentiev ( at UIUC.


  1. Lubensky, D.K. and D.R. Nelson. 1999. Driven polymer translocation through a narrow pore. Biophys. J. 77:1824-1838.
  2. Mathé, J., A. Aksimentiev, D.R. Nelson, K. Schulten and A. Meller. 2005. Orientation discrimination of single-stranded DNA inside the alpha-hemolysin membrane channel. Proc Natl Acad Sci USA 102(35):12377-12382.
  3. Lua and A. Grossberg, 2005 Phys. Rev. E 061918
DNA orientation
Figure 1

Figure 2

A-HL orientation

Figure 3